Structural and Biochemical Effects of Plumbagin on Sofosbuvir-induced Renal Cortical Injury in Rats: Role of Tumor Necrosis Factor-Alpha, Interleukin-6, JAK2/STAT3, and Nuclear Factor Kappa B-induced Inflammation

Abstract

Hepatitis caused by virus C results in serious health complications. Sofosbuvir is effective for treating hepatitis C but, with side effects especially on kidneys. Plumbagin is a natural plant with a powerful anti-inflammatory effect. The assessment of plumbagin effect on the renal cortical damage in rats induced by sofosbuvir, by assessing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), JAK2/STAT3 and nuclear factor kappa B (NF-κB). Forty adult rats (250–300 g) were divided into: group 1 (control); Group 2 received sofosbuvir 36 mg/kg; Group 3 received sofosbuvir and low dose of plumbagin (5 mg/kg); Group 4 received sofosbuvir and mid-dose of plumbagin (10 mg/kg); Group 5 received sofosbuvir and high dose of plumbagin (20 mg/kg); and Group 6 (sofosbuvir recovery). Drugs were taken once daily orally for 8 weeks. Blood samples were collected for the assessment of renal functions and serum TNF-α and IL-6. Renal specimens were processed for both measuring tissue JAK2/STAT3 levels and for histological and immunohistochemical studies. Group 2 showed a significant rise of blood urea and serum creatinine, serum TNF-α and IL-6, tissue JAK2/STAT3, hematoxylin and eosin significant histopathological changes, significant increase of collagen area density at Masson’s trichrome and significant rise of NF-κB-positive cells. Plumbagin treated groups showed dose-dependent amelioration of the preceding results. The recovery group showed partial recovery. Plumbagin has an ameliorating dose-dependent effect against sofosbuvir-induced renal cortical damage in rats rather than those left to recover alone through its antiinflammatory action. Hence, plumbagin could be promising for the treatment of different inflammatory diseases.