Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats

Alcaraz-Contreras, Yolanda; Mendoza-Lozano, RP; Martínez-Alcaraz, ER; Martínez-Alfaro, Minerva; Ma, Guansheng; Ramírez‐Morales, Marco Antonio; Vázquez-Guevara, M. A.

doi:10.1177/0960327115591373

Cited by 30 publications

(14 citation statements)

References 32 publications

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“…This result is in accordance with previous findings, whereas a significant increase and a marked decrease in renal relative weight were reported under Pb intoxication. Tissue accumulation of Pb resulted in a marked renal histopathological changes confirming recent data showing similar or more pronounced structural kidney injury under Pb effect …”

Section: Discussionsupporting

confidence: 88%

Thymoquinone attenuates lead‐induced nephropathy in rats

Mabrouk

2018

J Biochem & Molecular Tox

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Kidney hazards from lead (Pb) exposure are one of the fastest growing areas of concern in toxicology today. The thymoquinone (TQ) renoprotective effect against Pb‐induced nephropathy has not previously been studied. Therefore, adult male Wistar rats were treated with Pb (2000 ppm of Pb acetate in drinking water) and/or TQ (5 mg/kg/day, per os). All treatments were applied for 5 weeks. The results indicated that Pb exposure produced metal deposition, histopathological changes, functional impairment (significant elevation in plasma urea, uric acid, and creatinine levels), total antioxidant status decrease, and lipid peroxidation stimulation in the kidneys. Interestingly, TQ supplementation remarkably improved the Pb‐induced renal adverse effects without significantly reducing the tissue metal accumulation. In conclusion, our data indicate for the first time a protective effect of TQ against Pb‐induced nephropathy, most likely through an antioxidant mechanism. On this basis, TQ deserves more consideration and further examination as a potential therapeutic option.

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Section: Discussionsupporting

confidence: 88%

Thymoquinone attenuates lead‐induced nephropathy in rats

Mabrouk

2018

J Biochem & Molecular Tox

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“…Normal control (NC) and triptolide (TP) groups received oral administration of normal saline (1 ml/100 g), whereas silymarin-treated groups were orally administrated with silymarin (50, 100 and 200 mg/kg) dissolved in 0.5% CMC-Na distilled water. The doses of silymarin employed in the present study were based on our prior trial and previous study ( 21 ). Following treatment with normal saline or silymarin for 7 consecutive days, all groups, excluding the NC group, were given TP (2 mg/kg) by intraperitoneal injection to establish the liver injury animal model.…”

Section: Methodsmentioning

confidence: 99%

Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats

Wang

Huang

et al. 2017

Mol Med Report

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Silymarin has been used in the treatment of a number of liver diseases for a long time, but its efficacy in preventing triptolide induced acute hepatotoxicity has not been reported previously. The present study aimed to assess the protective effect of silymarin against triptolide (TP)-induced hepatotoxicity in rats. Rats were orally administrated with silymarin (50, 100 and 200 mg/kg) for 7 days and received intraperitoneal TP (2 mg/kg) on the day 8. Hepatic injuries were comprehensively evaluated in terms of serum parameters, morphological changes, oxidative damage, inflammation and apoptosis. The results demonstrated that TP-induced increases in serum parameters, including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total cholesterol and γ-glutamyl transpeptidase, which were determined using a biochemical analyzer, and histopathological alterations and hepatocyte apoptosis as determined by hematoxylin and eosin and TUNEL staining, respectively, were prevented by silymarin pretreatment in a dose-dependent manner. TP-induced depletions in the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione S-transferase and catalase, and glutathione levels, were also significantly reversed by silymarin, as determined using specific kits. Additionally, silymarin dose-dependently exhibited inhibitory effects on malonaldehyde content in the liver. The production of proinflammatory cytokines was investigated using ELISA kits, and the results demonstrated that silymarin dose-dependently inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-1β in the liver. To determine the mechanism of silymarin, western blot analysis was performed to investigate the protein expression of phosphorylated (p)-p38 and p-c-Jun N-terminal kinase (JNK) of the TNF-α induced inflammatory response and apoptotic pathways. Silymarin significantly blocked p38 and JNK phosphorylation and activation. Additionally, the expression of the proapoptotic proteins cytochrome c, cleaved caspase-3 and Bcl-2-associated X was also reduced following treatment with silymarin, as determined by ELISA, western blotting and immunohistochemistry, respectively. In conclusion, silymarin was demonstrated to dose-dependently protect rat liver from TP-induced acute hepatotoxicity, with the high dose (200 mg/kg) achieving a superior effect. This protective effect may be associated with the improvement of antioxidant and anti-inflammatory status, as well as the prevention of hepatocyte apoptosis. Therefore, silymarin may have the potential to be applied clinically to prevent TP-induced acute hepatotoxicity.

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“…Silibinin is known to exhibit strong antioxidant activities and its protective effects against ROS have been demonstrated in different cell lines [41,42]. Protective effects of silibinin on DNA can be explained by scavenging of ROS [102,103]. DON-and ENNs-induced genotoxicity may be associated with the oxidative stress [67,74], while oxidative stress does not play a predominant role in the induction of DNA damage by AOH and AME [66].…”

Section: Protective Effects Of Silibinin Against Mycotoxin Genotoxicitymentioning

confidence: 99%

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Tran

Viktorová

Augustynkova

et al. 2020

Toxins

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Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.

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Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats

Cited by 30 publications

References 32 publications

Thymoquinone attenuates lead‐induced nephropathy in rats

Thymoquinone attenuates lead‐induced nephropathy in rats

Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

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