
==== Front
Toxicol Rep
Toxicol Rep
Toxicology Reports
2214-7500
Elsevier

S2214-7500(24)00102-1
10.1016/j.toxrep.2024.101719
101719
Article
Homeostatic changes of trace elements in diazinon toxicity in rat model: The beneficial role of resveratrol
Esfahani Maryam m.esfahani@umsh.ac.ir
a1
Mehri Fereshteh f.mehri@umah.ac.ir
b⁎2
a Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
b Nutrition Health Research Center, Center of Excellence for Occupational Health, Research Center for Health Sciences, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
⁎ Correspondence to: Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. f.mehri@umah.ac.ir
1 0000–0001-5718–7126- ORCID

2 0000–0003-0106–245X- ORCID

30 8 2024
12 2024
30 8 2024
13 10171910 3 2024
26 8 2024
27 8 2024
© 2024 Published by Elsevier B.V.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background and objectives

Diazinon (DZN) is a cholinesterase inhibitor widely used to relieve agricultural pests and upgrade the productivity of crops. Resveratrol (Res), as a phenolic plant compound, has a protective role against free radicals. This study intended to evaluate the impacts of Res on homeostatic disturbances induced by DZN in rats.

Method

Twenty-four Wistar rats (4 weeks) were randomly distributed into four groups of six animals each. The first group (control group) received corn oil. The second group (Res group) received orally Res (20 mg/kg. The third group (DZN group) received the oral DZN (70 mg/kg); the fourth group (Res plus DZN group) was treated simultaneously with DZN (70 mg/kg) and Res (20 mg/kg); for a period of 5 weeks. The serum, liver, kidney, and heart levels of the Copper (Cu), zinc (Zn), iron (Fe), selenium (Se), and magnesium (Mg) as main trace elements are measured.

Results

DZN treatment decreased significantly serum, liver, kidney, and heart levels of Cu, Zn, Fe, Se, and Mg in comparison with the control group. Res administration enhanced serum, liver, kidney, and content of heart elements compared to the DZN group.

Conclusions

These results suggested that Res could ameliorate the homeostatic imbalance induced by DZN. Res had a protective effect against DZN-provoking heart, renal, and hepatic toxicity in animal models.

Graphical Abstract

Highlights

• Diazinon (DZN) is a cholinesterase inhibitor used to relieve agricultural pests.

• Resveratrol (Res) plant compound has a protective role against free radicals.

• DZN treatment decreased significantly serum and tissue levels of Cu, Zn, Fe, Se, and Mg.

• Res administration enhanced serum, liver, kidney, and content of heart elements.

Keywords

Diazinon
Resveratrol
Liver injury
Heart injury
Kidney injury
Handling Editor: Prof. L.H. Lash
==== Body
pmc1 Introduction

Organophosphate pesticides (OPs) are the most successful common herbicides widely used in cultivation, domestics, veterinary medicine, and industries [24]. Many of these compounds are fat-soluble and easily absorbed by skin, oral mucosa, digestive, and respiratory tracts [22]. DZN, as prominent Ops, is extensively used worldwide for controlling plant pests. Also, DZN is a notable cause of health hazards in different countries [14]. The main mechanism of toxicity induced by DZN is the inhibition of acetylcholinesterase and the accumulation of acetylcholine in the cholinergic synapses which lead to cholinergic syndrome [27]. The evidence of many studies showed that oxidative stress is another mechanism for sub-chronic and chronic toxicity of DZN [37]. In addition to excessive production of reactive oxygen species, DZN can alter antioxidant and scavenger systems. Antioxidant administration may relieve DZN-induced toxicity. Res, a phytoalexin, is naturally found in grapes, peanuts, and etcetera. This polyphenolic compound has beneficial effects in antioxidant systems, anti-inflammatory systems, and trace elements balancing. Interestingly, previous studies confirmed the protective effect of Res in oxidative stress caused by DZN [27]. Antioxidant enzymes protect body cells from excessive free radicals, especially oxygen free radicals[32]. Trace elements are significant in the function and structures of these antioxidant enzymes [49]. Cu, Zn, Fe, Mg, and Se act as antioxidant enzyme cofactors and have a role in free radical trapping [28]. In vitro studies indicated hemostatic disturbances induced by pesticides [20], [39]. Considering the importance of trace elements in the antioxidant system, we conducted this research to evaluate the possibility of protective impacts of Res against change in levels of Zn, Cu, Fe, Se, and Mg induced by DZN in animal models.

2 Material and methods

2.1 Chemicals

We purchased The DZN (Merck Co., 99 % purity, Code: 075801) from the Agricultural Research, Education and Development Organization (AREDO) (Tehran, Iran). Besides, Res was provided from Sigma (St. Louis, MO, USA, Code: 339132). It is utilized high-quality analytical-grade chemicals and Elisa's kits from Kiazist (Tehran- Iran).

2.2 Animal and research protocol

We provided twenty-four healthy 4-year-old Male Wistar rats (200–250 gr) from the Animal Care Center, Hamadan University of Medical Sciences. Also, we directed the administration schedule according to the instruction published by the Review Board of Hamadan University of Medical Sciences with the code number (IR.UMSHA.REC.1401.170). Our research group maintained rats at a temperature of 21–23°C, humidity of 50±10 %and a 12 h light/12 h dark cycle. All rats were fed with a standard diet and water ad libitum. Ethical concerns handled all the procedures. The control group were treated with a vehicle based on our former research. The selective DZN dose was 70 mg/kg (equal to 1/5 of its LD50 (350 mg/kg) [36]. DZN (70 mg/kg) and Res (20 mg/kg)[48] were solvated in the corn oil and H2O, respectively. These compounds were administrated every day via gavage for four weeks. We divided all rats randomly into four groups (six animals in each group). The control group received corn oil. The DZN group received DZN (70 mg/kg). The Res group received Resveratrol (20 mg/kg), DZN plus Res group simultaneously received DZN and Res at defined doses (70 mg/kg and 20 mg/kg, respectively). After 24 hours following the last dose, animals were sacrificed under anesthesia by ketamine (87 mg/kg) and xylazine (13 mg/kg) injection[46]. After blood sampling, serum separated and froze at −80 until biomarkers evaluation. It is removed Heart, liver, and kidney tissues and washed in cold saline. Next, the tissues rapidly sored in liquid nitrogen and froze at −70 °C until measuring.

2.3 The trace element concentrations' assessment of heart, kidney, and liver tissue

It was submerged all containers in nitric oxide, then rinsed in ultrapure water. Finally dried in an oven. Microwave digestion system (Topex, Preekem Scientific Instruments Co., Ltd., Shanghai, China) was used for degrading of the heart, the liver, and kidney tissues. Following sample mineralization, the trace element levels were assessed. 0.1 g of tissue put in high-pressure Teflon vessels and concentrated HNO3 (3 ml), H2O2 (1 ml), and HClO4 (0.5 ml, ultrapure, Merck, Germany) were added. After sealing the vessels with a Teflon lid, they were put into the steel bombs (sealed with the same momentum). Microwave oven was used to heat mixture according to the following temperatures: 90°C/13 min, 120°C/13 min, 130°C/60 min, and 140°C/60 min. The solution was cooled at room temperature and quantitatively transferred to a flask of ultra-water (10 ml, Millipore Direct Q UV, Japan). Trace element levels evaluated by inductively coupled plasma-optical emission spectroscopy (ICP-OES); Spectro Genesis, Germany)[17]. The data of the ICP-OES condition are available in Table 1.Table 1 ICP-OES apparatus specifications and analytical conditions for the determination of elements.

Table 1Instrument	Spector genesis	
Nebulizer	Cross flow	
Plasma power	1380 W	
Coolnat flow	13.00 L/min	
Auxiliary flow	1.00 L/min	
Nebulizer flow	1.03 L/min	
Optic flush	Normal	
Measure strategy Best	SNR	
Reply	2	
Measure time	80 s	
Flush time	30 s	

2.4 Statistical analysis

Our research group partners statistically analyzed the results of all groups with the SPSS-20 software. Data were compared with a one-way analysis of variance (ANOVA) and Tukey posttest. The differences were statistically regarded as significant when the P-value was less than 0.05. The results were represented as mean ± standard error. A P-value less than 0.05 was regarded as statistically significant.

3 Results

3.1 Serum trace element levels

It was provided the measurement of Serum trace element concentrations in all groups. In the control group, serum levels of Cu, Fe, Zn, Mg, and Se were significantly higher than those in the DZN group (p less than 0.01). Also, Res treatment significantly could increase Cu and Se levels compared to the control group (p less than 0.05). The co-treatment of DZN and Res could increase serum levels of Cu, Fe, Se, and Zn in contrast with the DZN groups (p-value less than 0.05 and 0.01, respectively). Although serum Mg concentration was higher in the co-treatment of DZN and Res compared to the DZN groups, this difference was not statistically significant (Table 2).Table 2 The effects of RES on serum Cu, Fe, Zn, Mg, Se level of Rats treatment with Diazinon (70 mg/kg).

Table 2Parameters
(mg/l)	Control	DZN	Res	DZN+ Res
(20 mg)	
Cu	2.46±0.03**	2.11±0.04	2.55±0.09***	2.29±0.07*	
Fe	10.89±1.17***	6.4±0.66	10.66±0.56***	8.86±0.58*	
Zn	16.04±1.61***	8.59±1.3	16.95±1.22***	13.52±0.58**	
Mg	67.4±2.12**	53.92±3.54	62.15±2.63*	56.79±2.06	
Se	7.21±0.02**	6.68±0.08	7.51±0.19***	7.12±0.24*	
Data are indicated as the mean ±standard error of 6 separate animals in each group. copper (Cu); zinc (Zn); iron (Fe); selenium (Se); magnesium (Mg); DZN: the group administrated Diazinon (70 mg/kg); Res: the group administrated Resveratrol (20 mg/kg); DZN+Res: the group administrated 70 mg/kg of Diazinon, after an hour 20 mg/kg of Res *p˂0.05 (compared to DZN group); **p˂0.01 (compared to DZN group); *** p˂0.001 (compared to DZN group).

3.2 Heart level of Trace element levels

As indicated in the (Table 3) control group, the heart levels of Cu, Mg, Zn, Mg, Fe, and Se were higher than those of the DZN group (Cu and Mg; p value less than 0.01 and Zn, Fe, Se; p value less than 0.001). The heart tissue levels of Fe and Zn in the DZN plus Res group were significantly higher than those in the DZN group (Fe and Zn; p value less than 0.05 and Se; p value less than 0.01). The heart Mg and Cu concentrations were not indicate statistical significant differences.Table 3 The effects of RES on heart Cu, Fe, Zn, Mg, Se level of Rats treatment with Diazinon (70 mg/kg).

Table 3Parameters
(mg/l)	Control	DZN	Res	DZN+Res
(20 mg)	
Cu	4.49±0.18**	3.54±0.35	4.25±0.09*	4.11±0.14	
Fe	44.57±1.53***	33.53±0.98	42.9±2.54**	38.42±1*	
Zn	9.75 ±0.45 ***	6.71±0.12	0.13±0.02***	8.14±0.76*	
Mg	177.48±2.1**	153.92±3.54	164.25±0.98**	152.51±2.09	
Se	10.58±0.41***	8.11±0.2	9.68±0.1***	9.17±0.11**	
Data are indicated as the mean ±standard error of 6 separate animals in each group. Data are indicated as the mean ±standard error of 6 separate animals in each group. copper (Cu); zinc (Zn); iron (Fe); selenium (Se); magnesium (Mg); DZN: the group administrated Diazinon (70 mg/kg); Res: the group administrated Resveratrol(20 mg/kg); DZN+Res: the group administrated 70 mg/kg of Diazinon, after an hour 20 mg/kg of Res *p˂0.05 (compared to DZN group); **p˂0.01 (compared to DZN group); *** p˂0.001 (compared to DZN group).

3.3 Liver level of trace element levels

According to Table 4, the mean levels of Cu (P value less than 0.001), Zn (P value less than 0.05), Mg (P value less than 0.01), and Se (P value less than 0.01)) in the control group were significantly higher than those of the DZN group. In the liver of the DZN group, the iron level was higher than that of the control group. The Res treatment could increase Cu (P value less than 0.001), Fe (P value less than 0.01), Zn, Mg, and Se (P value less than 0.001) in comparison with the DZN group. Also, DZN plus Res treatment could increase Cu, Zu, Mg (P value less than 0.01), and Se (P value less than 0.05) compared to the DZN group. Liver Fe level was not significantly different between DZN and DZN plus Res groups.Table 4 The effects of RES (20 mg/kg) on liver Cu, Fe, Zn, Mg, Se level of Rats treatment with Diazinon (70 mg/kg).

Table 4Parameters
(mg/l)	Control	DZN	Res	DZN+Res
(20 mg)	
Cu	3.98±0.09***	2.67 ±0.11	4.21 ±0.18***	3.14±0.1**	
Fe	98.09±0.24*	109.77±5.15	92.15±3.73**	114.63±0.51	
Zn	20.25±1.01*	18.13± 0.26	23.15±1.01***	21.3 ±0.33**	
Mg	176.43±3.02**	150.92±3.06	184.58±3.76***	163.18±4.01**	
Se	11.75±0.49**	9.04±0.17	12.56±0.45***	10.66±0.44*	
Data are indicated as the mean ±standard error of 6 separate animals in each group. Data are indicated as the mean ±standard error of 6 separate animals in each group. Copper (Cu); zinc (Zn); iron (Fe); selenium (Se); magnesium (Mg); DZN: the group administrated Diazinon (70 mg/kg); Res: the group administrated Resveratrol (20 mg/kg); DZN+Res: the group administrated 70 mg/kg of Diazinon, after an hour 20 mg/kg of Res *p˂0.05 (compared to DZN group); **p˂0.01 (compared to DZN group); *** p˂0.001 (compared to DZN group).

3.4 Renal trace element levels

The result of kidney trace element levels is indicated in Table 5. The renal Mg and Se levels in the DZN group were significantly lower than those in the control group (p-value less than 0.05). Also, Cu, Zn, and Fe concentrations were reduced in the group treated with DZN compared with the control group (p value less than 0.01, p value less than 0.001, respectively). On the other hand, Res treatment increased Cu, Mg, Zn, Mg, Fe, and Se concentrations compared with the control group (p value less than 0.05). Additionally, in the DZN co-treatment with the Res group, the concentration of Cu and Zn were considerably higher than those in the DZN group (p value less than 0.05 and p value less than 0.01, respectively). Although Fe, Se, and Mg levels decreased in the DZN group, these differences were not statistically significant.Table 5 The effects of RES on kidney Cu, Fe, Zn, Mg, Se level of Rats treatment with Diazinon (70 mg/kg).

Table 5Parameters
(mg/l)	Control	DZN	Res	DZN+Res
(20 mg)	
Cu	5.55±0.48**	4.09±0.13	5.13±0.21*	4.91±0.11*	
Fe	58.14±1***	48.23±1.01	52.20±1.54*	50.11±0.55	
Zn	9.42±0.22**	8.36±0.11	10.21± 0.08***	9.37±0.2**	
Mg	157.81±2.53*	145.92±3.04	166.25±5.54**	151.72±1.48	
Se	14.89±0.58*	12.81±1.03	17.31±0.59***	13.66±0.54	
Data are indicated as the mean ±standard error of 6 separate animals in each group. Data are indicated as the mean ±standard error of 6 separate animals in each group. Data are indicated as the mean ±standard error of 6 separate animals in each group. Copper (Cu); zinc (Zn); iron (Fe); selenium (Se); magnesium (Mg); DZN: the group administrated Diazinon (70 mg/kg); Res: the group administrated Resveratrol(20 mg/kg); DZN+Res: the group administrated 70 mg/kg of Diazinon, after an hour 20 mg/kg of Res *p˂0.05 (compared to DZN group); **p˂0.01 (compared to DZN group); *** p˂0.001 (compared to DZN group).

4 Discussion

In previous studies, we assessed the advantageous impact of Res on DZN-induced oxidative stress and inflammation in rat models [27], [15]. It is proved diverse health benefical impacts of Res on pathological condition including neurological disease and cognitive performance, diabetes, cancer, cardiovascular disease. Importantly, oxidative stress and inflammation have major function in these disturbances[38].Several studies reported the protective impact of Res on trace element content [32], [42]. DZN has multiorgan toxicity by means of oxidative stress induction in crucial tissues including brain, cardio vascular system, hepatic tissue, renal tissue and spleen [34]. As we know, there is no data on the impact of Res on tissue content of trace elements in DZN toxicity. Various studies have indicated that Ops toxicity could alter tissue trace element levels and ameliorate these changes [10]. In vivo and in vitro research confirmed the importance of oxidative stress in the pathophysiology of DZN-induced tissue injuries [12], [32]. Oxidative stress induced by DZN toxicity has impacts on various bio systems such as kidney, liver, heart or even hemopoietic organs and hemathological systems(decrease in hemoglobin level, the count of RBC and WBC [3]. It is noted that oxidative stress can stimulate RBC apoptosis or eryptosis. Also WBC and platelets can perceive oxidative stress mediators and aggressive oxidative stress status by ROS generation [9]. Some Trace elements have a prominent role in metabolic hemostasis regulation and antioxidant balance [43]. Zn is an essential component in various enzymes and transcription factors. This element has a significant function in glutathione peroxidase (GPX) regulation and metallothionein expression. Also it has a role in super oxide dismutase (SOD) structure. Zn affects glutamate-cystein ligase expression which is involved in glutathione synthesis [23]. Metal transcription factor 1 (MTF-1) as a Zn-dependent transcription factor modulates the expression of genes involved in anti-oxidative pathways [18]. The studies proved that Zn supplementation in chlorpyrifos-treated animals could moderate free radical production and lipid peroxidation. This was mediated by antioxidant improvement, including Glutathione (GSH) and glutathione S-transferase (GST). Human studies concluded that Zn deficiency has a function in delayed polyneuropathy induced by Ops [1]. Cu has various roles in biological and antioxidant systems, including SOD, ceruloplasmin (a ferroxidase that act as an antioxidant), and lysyl oxidase (necessary for extracellular matrixes stabilization)[41]. SOD is a noteworthy antioxidant enzyme which can eliminate toxic superoxide anions. The activity of this enzyme is dependent on active metal ions, including Cu and Zn [29]. DZN treatment can diminish SOD activity which is attributed to mitochondrial superoxide radical generation [13]. In this study, our findings statistically marked differences in Cu and Zn content in different tissues among the DZN administrated group and the control group. Se is a key component in antioxidant defense particularly TAC (total antioxidant capacity) which can evaluate the content of total antioxidants [8].Our former studies showed the reducing effect of DZN on TAC [15]. GPx is an antioxidant enzyme that can protect membrane lipids and macromolecules against ROS-induced oxidative damage. It is well-known that the GPX activity is dependent on selenium, an element incorporated in GPx [25].Our former studies indicated that DZN exposure caused a significant decrease in GPx activity [27]. In this study, we observed that Se concentrations decreased in the heart, liver, kidney, and serum of rats administered DZN. In line with this study, Cemeka et al., and Nisar Ahmad et al., reported that fenthion and chlorpyriphos (as OPs) diminish GPx levels in some tissues such as the heart, kidney, and liver [11], [35]. In vitro studies indicated that DZN exposure caused reproductive toxicity and DNA damage [47]. It is documented that Se can protect against DNA damage induced by DZN [21]. Also, animal studies presented protective effects of Se against hepatotoxicities associated with DZN exposure [31]. Iron is an important cofactor for catalase (CAT), proline, and lysyl hydroxylases, which have functions in collagen cross-linking. CAT as an important antioxidant enzyme, contains a prosthetic group of heme (ferric protoporphyrin IX) which is involved in reaction with H2O2. This enzyme is found in the peroxisomes [11], [33]. It is documented that DZN hurts CAT activity [26]. Consistent with our previous studies [27]. Ju-Hai et al. [39] and Baltaci et al., [7] found that DZN treatment meaningfully decreased Fe content compared with the control group. Mg, as the most important divalent intercellular cation, has an antioxidant impact via enzymatic mechanisms. This element can intensify the expression and activity of antioxidant enzymes such as SOD, CAT [16] and glutathione peroxidase [30]. Also, Mg functions as a cofactor of various enzymes which involved in cell membrane steadiness. It is indicated that hypomagnesemia has an association with further stages of oxidative stress; low level of tissue Mg content involves more hydrogen peroxide and superoxide production. Gorelick et al. reported supplementation with Mg reduced lipid peroxidation in animal models of Mg deficiency [6]. In the serum and other studied organs of the group of rats which received resveratrol the imbalance of studied trace elements changed to normalize, showing the beneficial role of resveratrol. Several studies investigated the protective effect of some supplements with ant oxidative characteristics in Ops toxicities [11], [35]. Res, as a natural phenolic compound, has attracted high attention because of hindering free radical reactions, including neutralizing free radicals [44]. Also, Res can enhance cellular defense via an increase in activity and gene expression of antioxidant enzymes [5], [19], [32]. Our previous study represented that Res treatment could improve hepatic and renal oxidative stress induced by DZN through enhancement of TAC, SOD, and CAT activities (CAT) [24]. Several studies confirmed the beneficial function of Res on homeostatic changes of trace elements [32]. In the current study, Res could restore some trace elements, including Zn, Se, Mg and in the kidney, liver, and tissue of rats exposed to DZN. Muselin et al. showed the protecting impact of Res on Cu, Zn, Fe, Mn, and Mg levels against toxicity induced by Aluminum [32]. Also, Abolaji et al. proved the beneficial effect of Res on Sodium Fluoride toxicity [2]. Cerebral ischemia caused oxidative stress via ROS overproduction. Ju-Hai Ro indicated that Res administration had a neuroprotective effect on oxidative stress status induced by cerebral ischemia. These effects were mediated via the modulation of trace elements with antioxidant properties, including Mg, Zn, and Se [40].Valko M [45] and He Y [20] indicated that Res treatment had a protection impact on cardiac cells against endoplasmic reticulum via elevation of intercellular Zn level. In vitro studies revealed that these effects are mediated via The transient potential receptor melastatin-2 (TRPM2) channel modulating [4]. Zhang e, al showed that Res administration increased renal se levels in arsenic exposure [50]. Ro, Ju-Hai pointed out that Res increased antioxidant activity (SOD and CAT) and Se levels in the brain tissue of rat animals [39]. It is suggested that Res can preserve Se level [39].

5 Conclusion

Some trace elements, including Zn, Cu, Se, Mg, and Fe, are prominent in antioxidant enzymes’ function or even structure. So it is critical to maintain trace element balances. As noted above, Res protects against DZN-induced oxidative stress via antioxidant activity enhancement and diminishing oxidative markers. It is concluded that Res can alter trace element levels, these effect show the other protective effects of this natural polyphenol against DZN toxicity. However, the exact mechanisms remain to be more clarified.

Compliance with ethical standards

Informed consent forms were signed by all the participants. Approval from the Institutional Research Board has been taken to conduct the study.

CRediT authorship contribution statement

Maryam Esfahani: Writing – review & editing. Fereshteh Mehri: Writing – original draft.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Data will be made available on request.

Acknowledgment

This work was supported by the Vice Chancellor for Research and Technology at Hamadan University of Medical Sciences (Grant No. 140104142545 ).

Author contributions

FM designed the study and interpreted the data. M.S. conducted the in vitro experiments. FM drafted the article, and MS revised it critically and finally approved the version to be submitted.
==== Refs
References

1 Abass M.A. Arafa M.H. Elfakharany Y.M. Atteia H.H. Role of zinc deficiency in the susceptibility to delayed polyneuropathy in organophosphorus intoxicated patients in zagazig university hospitals, Zagazig, Egypt Egypt. J. Forensic Sci. Appl. Toxicol. 16 Supplement 2019 17 33
2 Abolaji A.O. Ajala V.O. Adigun J.O. Adedara I.A. Kinyi H.W. Farombi E.O. Protective role of resveratrol, a natural polyphenol, in sodium fluoride-induced toxicity in Drosophila melanogaster Exp. Biol. Med. 244 18 2019 1688 1694
3 Ajibade T.O. Oyagbemi A.A. Omobowale T.O. Asenuga E.R. Afolabi J.M. Adedapo A.A. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid Interdiscip. Toxicol. 9 2 2016 66 77 28652848
4 Akyuva Y. Nazıroğlu M. Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel Sci. Rep. 10 1 2020 6449 32296107
5 Al Dera H.S. Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats Saudi Med. J. 37 4 2016 369 27052279
6 Arancibia-Hernández Y.L. Hernández-Cruz E.Y. Pedraza-Chaverri J. Magnesium (Mg2+) deficiency, not well-recognized non-infectious pandemic: origin and consequence of chronic inflammatory and oxidative stress-associated diseases Cell Physiol. Biochem 57 S1 2023 1 23
7 Baltaci A.K. Arslangil D. Mogulkoc R. Patlar S. Effect of resveratrol administration on the element metabolism in the blood and brain tissues of rats subjected to acute swimming exercise Biol. Trace Elem. Res. 175 2017 421 427 27392953
8 Binti Othman F. bin Jan Mohamed H.J. Sirajudeen K. Rajab N.F. The influence of selenium status on body composition, oxidative DNA damage and total antioxidant capacity in newly diagnosed type 2 diabetes mellitus: a case-control study J. Trace Elem. Med. Biol. 43 2017 106 112 28065595
9 Bissinger R. Bhuyan A.A.M. Qadri S.M. Lang F. Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases FEBS J. 286 5 2019 826 854 30028073
10 Cemek M. Büyükokuroğlu M.E. Büyükben A. Aymelek F. Özcan L. Effects of vitamin E and selenium on tissue bio-element status in organophosphate toxicity of rats Pestic. Biochem. Physiol. 98 1 2010 9 18
11 Cemek M. Büyükokuroğlu M.E. Yürümez Y. Yavuz Y. Aslan A. Büyükben A. Aymelek F. Tissue trace and major element levels in organophosphate insecticide fenthion (Lebaycid®) toxicity in rats: prophylactic and therapeutic effect of exogenous melatonin Ecotoxicol. Environ. Saf. 73 2 2010 206 212 19800688
12 Chen C. Jiang X. Hu Y. Zhang Z. The protective role of resveratrol in the sodium arsenite-induced oxidative damage via modulation of intracellular GSH homeostasis Biol. Trace Elem. Res. 155 2013 119 131 23884857
13 El-Shenawy N.S. El-Salmy F. Al-Eisa R.A. El-Ahmary B. Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver Pestic. Biochem. Physiol. 96 2 2010 101 107
14 Esfahani M. Rahbar A.H. Soleimani Asl S. Mehri F. Resveratrol: a panacea compound for diazinon-induced renal toxicity Toxin Rev. 2021 1 11
15 Esfahani M. Rahbar A.H. Soleimani Asl S. Mehri F. Resveratrol: a panacea compound for diazinon-induced renal toxicity Toxin Rev. 42 1 2023 40 50
16 Faiz S. Yasin N.A. Khan W.U. Shah A.A. Akram W. Ahmad A. Ali A. Naveed N.H. Riaz L. Role of magnesium oxide nanoparticles in the mitigation of lead-induced stress in Daucus carota: modulation in polyamines and antioxidant enzymes Int. J. Phytoremediat. 24 4 2022 364 372
17 Fallah A.A. Saei-Dehkordi S.S. Nematollahi A. Jafari T. Comparative study of heavy metal and trace element accumulation in edible tissues of farmed and wild rainbow trout (Oncorhynchus mykiss) using ICP-OES technique Microchem. J. 98 2 2011 275 279
18 Grzywacz A. Gdula-Argasińska J. Muszyńska B. Tyszka-Czochara M. Librowski T. Opoka W. Metal responsive transcription factor 1 (MTF-1) regulates zinc dependent cellular processes at the molecular level Acta Biochim. Pol. 62 3 2015 491 498 26336656
19 Hammoud G.M. Shalaby R.A. Experimental evaluation of protective action of resveratrol against aluminum-induced toxicity in male rats Int. J. Adv. Res. Biol. Sci. 6 1 2019 11 24
20 He Y. Fu Y. Xi M. Zheng H. Zhang Y. Liu Y. Zhao Y. Xi J. He Y. Zn2+ and mPTP mediate resveratrol-induced myocardial protection from endoplasmic reticulum stress Metallomics 12 2 2020 290 300 31872196
21 Kashanian S. Gholivand M.B. Ahmadi F. Ravan H. Interaction of diazinon with DNA and the protective role of selenium in DNA damage DNA Cell Biol. 27 6 2008 325 332 18447756
22 Kheiripour N. Plarak A. Heshmati A. Asl S.S. Mehri F. Ebadollahi-Natanzi A. Ranjbar A. Hosseini A. Evaluation of the hepatoprotective effects of curcumin and nanocurcumin against paraquat-induced liver injury in rats: Modulation of oxidative stress and Nrf2 pathway." J. Biochem. Mol. Toxicol. 35 5 2021 e22739
23 Marreiro D.D.N. Cruz K.J.C. Morais J.B.S. Beserra J.B. Severo J.S. De Oliveira A.R.S. Zinc and oxidative stress: current mechanisms Antioxidants 6 2 2017 24 28353636
24 Mehri F. Jenabi E. Bashirian S. Shahna F.G. Khazaei S. The association between occupational exposure to silica and risk of developing rheumatoid arthritis: a meta-analysis Saf. Health Work 11 2 2020 136 142 32596007
25 Mehri F. Rahbar A.H. Ghane E.T. Souri B. Esfahani M. Changes in oxidative markers in COVID-19 patients Arch. Med. Res. 52 8 2021 843 849 34154831
26 Mehri F. Ranjbar A. Shirafkan N. Asl S.S. Esfahani M. The protective effect of resveratrol on diazinon-induced oxidative stress and glucose hemostasis disorder in rats' liver." J. Biochem. Mol. Toxicol. 2022 e23063
27 Mehri F. Ranjbar A. Shirafkan N. Asl S.S. Esfahani M. The protective effect of resveratrol on diazinon-induced oxidative stress and glucose hemostasis disorder in rats' liver." J. Biochem. Mol. Toxicol. 36 7 2022 e23063
28 Méplan C. Trace elements and ageing, a genomic perspective using selenium as an example J. Trace Elem. Med. Biol. 25 2011 S11 S16 21145717
29 Mondola P. Damiano S. Sasso A. Santillo M. The Cu, Zn superoxide dismutase: not only a dismutase enzyme Front. Physiol. 7 2016 594 27965593
30 Morais J.B.S. Severo J.S. Santos L.R. d de Sousa Melo S.R. de Oliveira Santos R. de Oliveira A.R.S. Cruz K.J.C. do Nascimento Marreiro D. Role of magnesium in oxidative stress in individuals with obesity Biol. Trace Elem. Res. 176 2017 20 26 27444303
31 Mossa A.-T.H. Heikal T.M. Omara E.A.A. Liver damage associated with exposure to aspirin and diazinon in male rats and the ameliorative effect of selenium Biomed. Aging Pathol. 4 2 2014 137 145
32 Muselin F. Gârban Z. Cristina R.T. Doma A.O. Dumitrescu E. Vițălaru A.B. Bănățean-Dunea I. Homeostatic changes of some trace elements in geriatric rats in the condition of oxidative stress induced by aluminum and the beneficial role of resveratrol J. Trace Elem. Med. Biol. 55 2019 136 142 31345351
33 Nandi A. Yan L.-J. Jana C.K. Das N. Role of catalase in oxidative stress-and age-associated degenerative diseases Oxid. Med. Cell. Longev. 2019 2019
34 Navaei-Nigjeh M. Daniali M. Rahimifard M. Khaksar M.R. Multi-organ toxicity attenuation by cerium oxide and yttrium oxide nanoparticles: comparing the beneficial effects on tissues oxidative damage induced by sub-acute exposure to diazinon Pharm. Nanotechnol. 8 3 2020 225 238 32767961
35 Nisar N.A. Sultana M. Waiz H.A. Para P.A. Baba N.A. Zargar F.A. Raja W.H. Experimental study on the effect of vitamin C administration on lipid peroxidation and antioxidant enzyme activity in rats exposed to chlorpyriphos and lead acetate Vet. World 6 8 2013 461
36 Pakzad M. Fouladdel S. Nili-Ahmadabadi A. Pourkhalili N. Baeeri M. Azizi E. Sabzevari O. Ostad S.N. Abdollahi M. Sublethal exposures of diazinon alters glucose homostasis in Wistar rats: biochemical and molecular evidences of oxidative stress in adipose tissues Pestic. Biochem. Physiol. 105 1 2013 57 61 24238291
37 Rahbari A. Nazem H. Fazilati M. Mehri F. Protective effect of resveratrol against sub-acute diazinon-induced oxidative stress in rat kidney Koomesh 23 6 2021 794 800
38 Ramírez-Garza S.L. Laveriano-Santos E.P. Marhuenda-Muñoz M. Storniolo C.E. Tresserra-Rimbau A. Vallverdú-Queralt A. Lamuela-Raventós R.M. Health effects of resveratrol: results from human intervention trials Nutrients 10 12 2018 1892 30513922
39 Ro J.-H. Liu C.-C. Lin M.-C. Resveratrol mitigates cerebral ischemic injury by altering levels of trace elements, toxic metal, lipid peroxidation, and antioxidant activity Biol. Trace Elem. Res. 199 10 2021 3718 3727 33230635
40 Ro J.-H. Liu C.-C. Lin M.-C. Resveratrol mitigates cerebral ischemic injury by altering levels of trace elements, toxic metal, lipid peroxidation, and antioxidant activity Biol. Trace Elem. Res. 199 2021 3718 3727 33230635
41 Rucker R.B. Kosonen T. Clegg M.S. Mitchell A.E. Rucker B.R. Uriu-Hare J.Y. Keen C.L. Copper, lysyl oxidase, and extracellular matrix protein cross-linking Am. J. Clin. Nutr. 67 5 1998 996S 1002S 9587142
42 Shumakova A.A. Shipelin V.A. Leontyeva E. Gmoshinski I.V. Effect of Resveratrol, l-Carnitine, and aromatic amino acid supplements on the trace element content in the organs of mice with dietary-induced obesity Biol. Trace Elem. Res. 200 1 2022 281 297 33624220
43 Skalny A.V. Aschner M. Silina E.V. Stupin V.A. Zaitsev O.N. Sotnikova T.I. Tazina S.I. Zhang F. Guo X. Tinkov A.A. The role of trace elements and minerals in osteoporosis: a review of epidemiological and laboratory findings Biomolecules 13 6 2023 1006 37371586
44 Truong V.L. Jun M. Jeong W.S. Role of resveratrol in regulation of cellular defense systems against oxidative stress Biofactors 44 1 2018 36 49 29193412
45 Valko M. Jomova K. Rhodes C.J. Kuča K. Musílek K. Redox-and non-redox-metal-induced formation of free radicals and their role in human disease Arch. Toxicol. 90 2016 1 37 26343967
46 Veilleux-Lemieux D. Castel A. Carrier D. Beaudry F. Vachon P. Pharmacokinetics of ketamine and xylazine in young and old Sprague–Dawley rats." J. Am. Assoc. Lab. Anim. Sci. 52 5 2013 567 570 24041212
47 Wang W. Luo S.-M. Ma J.-Y. Shen W. Yin S. Cytotoxicity and DNA damage caused from diazinon exposure by inhibiting the PI3K-AKT pathway in porcine ovarian granulosa cells J. Agric. Food Chem. 67 1 2018 19 31 30525588
48 Wenzel E. Somoza V. Metabolism and bioavailability of trans-resveratrol." Mol. Nutr. Food Res. 49 5 2005 472 481 15779070
49 Wołonciej M. Milewska E. Roszkowska-Jakimiec W. Trace elements as an activator of antioxidant enzymes Adv. Hyg. Exp. Med. 70 2016 1483 1498
50 Zhang W. Liu Y. Ge M. Jing J. Chen Y. Jiang H. Yu H. Li N. Zhang Z. Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats Nutr. Res. Pract. 8 2 2014 220 226 24741408
