FK506-induced hepatotoxicity

BACKGROUND: Tacrolimus (FK506) is an immunosuppressive agent and has toxic side effects such as nephrotoxicity, hepatotoxicity, and neurotoxicity. In our study, we aimed to investigate the protective effect of silymarin on renal and hepatic toxicity considered to be tacrolimus related. METHODS: In this 6-week experimental study, 46 eight-week-old healthy male rats were used. The groups comprised the Control (healthy rats, n = 6), Tac (tacrolimus 1 mg/kg, n = 8), silymarin 100 mg/kg (SLI 100 mg/kg n = 8), Tac + SLI 100 (tacrolimus 1 mg/kg + SLI 100 n = 8), SLI 200 (SLI 200 mg/kg n = 8), and Tac + SLI 200 (tacrolimus 1 mg/kg + SLI 200 mg/kg n = 8)...

Pseudomonas aeruginosa Exotoxin A (PEA) induces hepatotoxicity in experimental animals. Lipopolysaccharide (LPS) interacts synergistically with xenotoxics to induce severe organ injury. We examined the combination of non-injurious doses of LPS and sub-hepatotoxic PEA in the induction of multiple organ injury (MOI). Rats treated with 20 or 40 microg/kg LPS plus 10 microg/kg PEA developed severe liver, kidney, and lung injury; elevation of TNF-alpha, IFN-gamma, and IL-2; and high mortality. Depletion of Kupffer cells or T-cells by pretreatment with Gadolinium Chloride or FK506, respectively, attenuated MOI...

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