Allopurinol Ameliorates Thioacetamide-Induced Acute Liver Failure by Regulating Cellular Redox-Sensitive Transcription Factors in Rats

Abstract

Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.

Allopurinol alleviates hypertension and proteinuria in high fructose, high salt and high fat induced model of metabolic syndrome

“…In addition, kidneys isolated from metabolic syndrome animals showed increased of TGF-β and TNFα expression, increased glutathione peroxidase enzyme activity and increased collagen deposition while allopurinol reduced the kidney level of TGF-β and suppressed collagen deposition. This is consistent with previous work with the ability of allopurinol to reduce the elevated liver TNFα levels associated with acute liver failure induced by thioacetamide in rats (40).…”

Allopurinol reduces antigen-specific and polyclonal activation of human T cells

“…Thus, allopurinol would deprive T cells from iROS which are required during the early activation of the NF-kB complex (Los et al, 1995) and PKC (Kang et al, 2006), thus promoting a hyporesponsive state of T cells. In agreement with this notion, allopurinol has been recently shown to reduce NF-κB pathway activation, pro-inflammatory cytokines production, and oxidative stress in different in vivo models of inflammation (Correa-Costa et al, 2011; Aldaba-Muruato et al, 2012; Demirel et al, 2012). …”

Inhibition of RKIP aggravates thioacetamide‑induced acute liver failure in mice

“…Acute hepatic injury was induced by TAA as previously described (8). In brief, 60 mice were divided into 4 groups (15 animals/group): Normal control, locostatin control, TAA model and TAA plus locostatin (TL) groups.…”