Syringic acid and silymarin concurrent administration inhibits sodium valproate‐induced liver injury in rats

Abstract

Sodium valproate (SV) is a well‐known anti‐epileptic drug, also used to control convulsions, bipolar disorders and migraines. SV has been shown to induce liver toxicity in clinical subjects. Syringic acid (SA), a natural polyphenolic compound has potential antioxidant, anti‐inflammatory and several beneficial effects. Therefore, in this study, we evaluated hepatoprotective effect of SA against SV‐induced liver injury in rats. Wistar rats were treated with SV orally at a dose of 500 mg/kg, once daily, for 14 days. Another three groups of rats were administered with SV and concurrently treated with SA (40 and 80 mg/kg) and silymarin (SIL) (100 mg/kg) for 14 days. SV administration for 14 days caused significant (p < .001) elevation of liver transaminases and ALP in serum. Liver MDA level was significantly (p < .001) increased with a concomitant decrease (p < .001) in enzymic antioxidants activities in SV administered rats. SV administration also caused the upregulation of proinflammatory markers such as tumor necrosis factor α, c‐Jun N‐terminal kinase, nuclear factor kappa B, cyclooxygenase‐2 and Interleukin 6 expressions in liver tissue. Histopathological studies also revealed the presence of inflammatory cell infiltration and hepatocellular necrosis upon SV administration. At both doses, concurrent administration of SA and SIL significantly (p < .001) inhibited the liver transaminase activities in serum, oxidative stress, and proinflammatory markers expression in liver tissue. Our current results suggest that SA can be a promising herbal drug that can inhibit SV‐induced hepatotoxicity when administered together due its potential anti‐inflammatory effects.

Effect of syringic acid on steroid and gonadotropic hormones, hematological indices, sperm characteristics and morphologies, and markers of tissue damage in methyl cellosolve-administered rats

“…Again, in this study, SYAC at all doses tested significantly decreased the serum activities of these enzymes, suggesting its hepatoprotective role against MTC-induced hepatotoxicity in rats. Our findings agree with previously published studies by Okkay et al [ 45 ] who reported the hepatoprotective effect of SYAC against thioacetamide-induced hepatic encephalopathy and Gheena et al [ 46 ] who reported the hepatoprotective effect of concurrent administrations of SYAC and silymarin against sodium valproate-induced liver injury in rats.…”

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis

“…Group II (liraglutide group) received daily liraglutide subcutaneous injection (200 μg/kg body weight) dissolved in normal saline for 4 weeks 10,11 . Group III (valproic acid‐treated group) was administrated sodium valproate (500 mg/kg) dissolved in distilled water (0.5 mL) via oral gavage for 2 weeks 12 . Group IV (combined valproic acid & liraglutide treated group) received the previously mentioned valproic acid dose plus liraglutide subcutaneously (200 μg/kg body weight) daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration.…”

Boldine protects against carbon tetrachloride‐induced chronic liver injury by regulating NF‐κB signaling pathway

“…Previous studies have also shown that both boldine and SIL have antioxidant and membrane stabilizing properties against various drugs and chemical induced liver injuries. [22,48,49] Therefore, it can be stated that boldine could have nullified CCl 4 mediated free radicals and reduced oxidative stress due to its inherent antioxidant and free radical quenching properties.…”