Silymarin Protects Mouse Liver and Kidney from Thioacetamide Induced Toxicity by Scavenging Reactive Oxygen Species and Activating PI3K-Akt Pathway

Abstract

Silymarin (SMN) has been shown to possess a wide range of biological and pharmacological effects. Besides, SMN has antioxidant and free radical scavenging activities. Thioacetamide (TAA) is a well-documented liver toxin that requires oxidative bioactivation to elicit its hepatotoxic effect which ultimately modifies amine-lipids and proteins. Our study has been designed in a TAA exposed mouse model to investigate whether SMN could protect TAA-induced oxidative stress mediated hepatic and renal damage. Results suggest that TAA generated reactive oxygen species (ROS), caused oxidative stress and induced apoptosis in the liver and kidney cells via JNK as well as PKC and MAPKs signaling. All these detrimental effects of TAA could, however, be suppressed by SMN which not only scavenged ROS but also induced PI3K-Akt cell survival pathway in the liver and prevented apoptotic pathways in both the organs. Histological studies, collagen staining and DNA fragmentation analysis also supported our results. Combining, we say that SMN possess beneficial role against TAA mediated hepatic and renal pathophysiology.

Protective and anti-inflammatory effects of silymarin on paraquat-induced nephrotoxicity in rats

“…Paraquat causes impaired renal function which is accompanied by reduction of the renal clearance rate and increasing of paraquat level, toxicity, and other organ dysfunctions (6,7). Administration of thioacetamide has been shown to induce liver and kidney injuries and silymarin ameliorated some parameters such as DNA fragmentation, nitric oxide, oxidative stress, collagen content, and liver and kidney histopathological changes in thioacetamide-induced toxicity (8). Silymarin is a potent antioxidant that can scavenge free radicals and ROS (9).…”

Hesperitin enhances the ability of daunorubicin by co-loading with MPEG-PCL nanoparticles to induce apoptosis in gastric cancer

“…The findings suggested that HE/DA/M nano-micelles showed specificity to be accumulated in tumor tissues. Additionally, the toxicity of HE/DA/M formulation in vivo was investigated through assessing essential hepatic and renal health indexes [26,30,66,67]. AST, ALT, BUN and CREA contents in mice with treatment of HE/DA/M nano-micelles were similar to that in the Con group, indicating that HE/DA/M nano-micelles caused no severe hepatic and kidney toxicity.…”

Protective effects of olive in renal failure; a review on current knowledge

“…Al-Attar et al studied the protective effects of olive leaf extract on nephrotoxicity of this substance in the kidneys of mice and proved that the levels of urea and serum creatinine in the group treated with olive leaf extract reduced, but not significantly. In terms of histological, the normality of the kidney structure was proved in the group treated with the extract (24,25).…”

“…Thioacetamide can be viewed as a hepatic toxin and carcinogen (24). The toxic complications of this compound are not only limited to the liver, but involve several organs such as the kidneys, spleen, lungs, intestines, and brain (24,25).…”

“…Thioacetamide can be viewed as a hepatic toxin and carcinogen (24). The toxic complications of this compound are not only limited to the liver, but involve several organs such as the kidneys, spleen, lungs, intestines, and brain (24,25). Al-Attar et al studied the protective effects of olive leaf extract on nephrotoxicity of this substance in the kidneys of mice and proved that the levels of urea and serum creatinine in the group treated with olive leaf extract reduced, but not significantly.…”