Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb- and paraquat-induced hepatotoxicity in rats

Ahmad, Israr; Shukla, Smriti; Kumar, Ashutosh; Singh, Brajesh Kumar; Kumar, Vinod; Chauhan, Amit; Singh, Dhirendra Kumar; Pandey, Harsh; Singh, Chetna

doi:10.1016/j.cbi.2012.10.027

Cited by 89 publications

(58 citation statements)

References 63 publications

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“…The administration of silymarin also significantly protected SOD and GSH-Px activities by directly scavenging ROS as well as by inhibiting lipid peroxidation. Ahmed et al [53]. Reported that the protective effects of silymarin are mediated, in part by its antioxidant defence ability and the scavenging of free radicals; It has been also shown that silymarin has the ability to chelate with redox metals and to reduce lipid peroxidation by induction of both enzymatic and non-enzymatic antioxidants [51,54].…”

Section: Discussionmentioning

confidence: 99%

Effect of Silymarin Extracted From Silybum Marianum on Nickel Hematotoxicity and Nephrotoxicity in Male Albino Wistar Rats

Bouhalit

Kechrid

Elfeki

2017

Int J Pharm Pharm Sci

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Objective: The objective of this study was to investigate the effect of silymarin extract from Silybum marianum against nickel-induced alterations in haematological indices, kidney dysfunction and renal antioxidant defence system. Methods:Male albino Wistar rats were divided into four groups seven each. Control, silymarin, nickel and nickel plus silymarin. Silymarin was administrated orally (100 mg/kg b. wt) and nickel as nickel sulfate (NiSO4 6H2 Results:The treatment with nickel led to a significant decrease in body weight with an increase in both absolute and relative kidney weights and a significant increase in renal markers, which confirmed by histopathological alteration. A microcytic anemia was also observed, which was manifested by a reduction of red blood cells count (RBC), hemoglobin (Hb) concentration, platelet counts (Plt), hematocrit and white blood cells counts (WBC). The level of lipid peroxidation was increased. Whereas, GSH concentration and enzymatic antioxidants SOD, GSH-Px and CAT activities were decreased. The co-treatment with methanolic extract of milk thistle attenuated the variation in the hematological and renal markers, decreasing renal lipid peroxidation (p<0.05) with a concomitant increasing reduced glutathione content (p<0.01) and restoring the antioxidant enzymes (SOD, CAT, GSH-Px) in kidney, as well as an improvement in histological changes compared to those previously noticed in nickel group. 0) was given intraperitoneally (20 mg/kg b. wt) at alternative days. The experiment continued for three consecutive weeks. Body weight was recorded regularly. After overnight fasting, animals were killed and serum creatinine, serum urea, serum uric acid, hematological parameters and renal antioxidant markers were determined. Conclusion:To conclude, these findings demonstrated that silymarin extract effectively improved heamatotoxicity and nephrotoxicity caused by nickel.

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Section: Discussionmentioning

confidence: 99%

Effect of Silymarin Extracted From Silybum Marianum on Nickel Hematotoxicity and Nephrotoxicity in Male Albino Wistar Rats

Bouhalit

Kechrid

Elfeki

2017

Int J Pharm Pharm Sci

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“…Moreover, this flavonoid has a phenolic structure, which allows electron donation to free radicals and reactive oxygen species (ROS) in order to stabilize them and prevents lipid peroxidation by interaction with intracellular glutathione (27,28). Additionally, silymarin has previously been reported to have anti-proliferative, anti-fibrotic, anti-apoptotic, antiviral and immunomodulatory properties (25,29) and has been shown to inhibit TNF-α expression (30). …”

Section: Introductionmentioning

confidence: 99%

Protective effects of silymarin against bisphenol A-induced hepatotoxicity in mouse liver

Zăuleţ

Kevorkian

Dinescu

et al. 2017

Experimental and Therapeutic Medicine

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Bisphenol A (BPA) is an endocrine-disrupting chemical released into the environment, with severe consequences for human health, including metabolic syndrome and associated pathological conditions. Due to limited information on BPA-induced hepatotoxicity, the present study focused on investigating the association between BPA-induced toxicity and inflammatory markers in the liver, and how these injuries may be alleviated using the natural agent silymarin, a flavonoid with antioxidant properties obtained from Silybum marianum. Administration of BPA to male CD-1 mice for 10 days caused a significant increase in the number of cells immunopositive for interleukin 6 and tumor necrosis factor-α, pro-inflammatory cytokines that mediate the hepatic inflammatory response. Treatment with 200 mg/kg of silymarin concurrently with BPA for 10 days resulted in a diminished level of pro-inflammatory cytokines and in significantly reduced ultrastructural injuries. Additionally, silymarin was able to restore the significantly decreased glycogen deposits observed following BPA exposure to normal levels, thus favoring hepatic glycogenesis. This study represents the first report of silymarin ability to reduce hepatic lesions and to counteract inflammation caused by BPA in mice. A dose of 200 mg/kg silymarin was sufficient to induce a protective effect against structural and ultrastructural injuries induced by BPA and to lower the levels of pro-inflammatory cytokines observed in murine liver tissue following exposure to BPA.

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“…Traditional antioxidants, such as vitamin C, N-acetylcysteine, and others for the treatment of PQ poisoning have been used clinically and have shown an effect. 23,24 In this study, we found that porous Se@SiO 2 nanospheres could alleviate oxidative stress and reduce inflammatory cytokine production in PQinduced ALI.…”

Section: Discussionmentioning

confidence: 59%

“…The PQ + Se@SiO 2 group was also treated with 1 mg/kg porous Se@SiO 2 nanospheres via intraperitoneal injection every 24 h. The concentration of porous Se@SiO 2 nanospheres was selected according to our previous research. 21 The PQ group and PQ + Se@SiO 2 group were randomly divided into 3 sub-groups according to differing times of examination (24,48 and 72 h) after PQ treatment. The rats were executed at the corresponding time points after injection of sodium pentobarbital (50 mg/kg).…”

Section: Animal Experimentsmentioning

confidence: 99%

Porous Se@SiO<sub>2</sub> nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

Zhu¹,

Deng²,

Ji³

et al. 2017

IJN

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Acute paraquat (PQ) poisoning is one of the most common forms of pesticide poisoning. Oxidative stress and inflammation are thought to be important mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge intracellular free radicals directly or indirectly. In this study, we investigated whether porous Se@SiO 2 nanospheres could alleviate oxidative stress and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells were used in this study. Rats were categorized into 3 groups: control (n=6), PQ (n=18), and PQ + Se@SiO 2 (n=18). The PQ and PQ + Se@SiO 2 groups were randomly and evenly divided into 3 sub-groups according to different time points (24, 48 and 72 h) after PQ treatment. Porous Se@SiO 2 nanospheres 1 mg/kg (in the PQ + Se@SiO 2 group) were administered via intraperitoneal injection every 24 h. Expression levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α and interleukin-1β were detected, and a histological analysis of rat lung tissues was performed. The results showed that the levels of ROS, malondialdehyde, NF-κB, p-NF-κB, tumor necrosis factor-α and interleukin-1β were markedly increased after PQ treatment. Glutathione and superoxide dismutase levels were reduced. However, treatment with porous Se@SiO 2 nanospheres markedly alleviated PQ-induced oxidative stress and inflammation. Additionally, the results from histological examinations and wet-to-dry weight ratios of rat lung tissues showed that lung damage was reduced after porous Se@SiO 2 nanosphere treatment. These data indicate that porous Se@SiO 2 nanospheres may reduce NF-κB, p-NF-κB and inflammatory cytokine levels by inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO 2 nanospheres may be a therapeutic method for use in the future for PQ poisoning.

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Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb- and paraquat-induced hepatotoxicity in rats

Cited by 89 publications

References 63 publications

Effect of Silymarin Extracted From Silybum Marianum on Nickel Hematotoxicity and Nephrotoxicity in Male Albino Wistar Rats

Effect of Silymarin Extracted From Silybum Marianum on Nickel Hematotoxicity and Nephrotoxicity in Male Albino Wistar Rats

Protective effects of silymarin against bisphenol A-induced hepatotoxicity in mouse liver

Porous Se@SiO<sub>2</sub> nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

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