Silibinin mitigates zidovudine-induced hepatocellular degenerative changes, oxidative stress and hyperlipidaemia in rats

Abstract

<jats:p> Prolonged zidovudine (AZT) treatment in HIV-infected and AIDS patients is shown to induce liver toxicity leading to complications. Therapeutic regimen that could encounter this adverse effect is unavailable and management of toxicity is often symptomatic or is limited to withdrawal of therapy. In the present investigation, we evaluated the alleviating properties of silibinin (SBN), a flavanolignan obtained from Silybum marianum against subacute AZT-induced hepatotoxicity and oxidative stress in rats. AZT treatment (50 mg/kg body weight (b.w.) periorally (p.o.), daily for 45 days) caused highly significant increases in alanine transaminase, alkaline phosphatase, argininosuccinic acid lyase and bilirubin in serum. Oxidative stress is shown by a highly significant increase in lipid peroxidase and total carbonyl content and decrease in catalase and protein thiols in the liver tissue. Hyperlipidaemia is indicated by highly significant increase in total lipids and free fatty acid in serum. Evaluation of liver by haematoxylin and eosin staining shows parenchymal cell enlargement, inflammatory changes and increase in sinusoidal spaces. Simultaneous treatment of SBN (100 mg/kg b.w. p.o., daily for 45 days) significantly protected the liver against hepatotoxicity, oxidative stress and hyperlipidaemia induced by AZT, and this alleviating property is attributed to hepatoprotective, membrane-stabilizing, antioxidant and free radical scavenging properties of SBN. </jats:p>

Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation

“…Silybin, the major active molecule of silymarin, is a very potent antioxidant compound capable of scavenging free radicals and ROS, and has been shown to exert neuroprotective (28–30), hepatoprotective (31,32) and anti-carcinogenic effects (33–35). It is now being used as a traditional medicine for the treatment of various liver disorders in China.…”

Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

“…In one study, polychlorinated biphenyls induced hepatotoxicity associated with increase in LDL, triglycerides and cholesterol after 30 days of continuous treatment [63] . Several authors have observed a pattern of increased lipid profile in response to drug induced liver toxicity [55] , [40] . The reason for an increase in lipid profile, during liver damage for e .…”

Azidothymidine induces severe hematological toxicity and hepatic injury in Charles Foster rats

“…16 In another study it was demonstrated that AZT treatment can cause hepatotoxicity in Wistar rats. 17 They reported highly significant increase in alanine transaminase, alkaline phosphatase, argininosuccinic acid lyase and bilirubin in serum of Wistar albino rats. In a similar kind of study it was reported that AZT can cause significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP).…”

“…17,29 Transaminases and ALP are considered important markers of hepatic injury because their increased level in blood serum is observed immediately post hepatic necrosis and hepatocellular membrane damage. 27,30 In the present study, AZT treated rodents showed a highly remarkable increase in ALT and ALP and these results are in agreement with the above report.…”