Protective effects of Althaea officinalis L. extract against N-diethylnitrosamine-induced hepatocellular carcinoma in male Wistar rats through antioxidative, anti-inflammatory, mitochondrial apoptosis and PI3K/Akt/mTOR signaling pathways.

Abstract

Hepatocellular carcinoma is the fourth cause of death due to cancer and includes 90% of liver tumors. Therefore, in this study, it was tried to show that Althaea officinalis L. flower extract (ALOF) can protect hepatocytes against N-diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Totally, 70 Wistar rats were divided into seven groups (n = 10/group) of sham, DEN, treatment with silymarin (SIL; DEN + SIL), treatment with ALOF (DEN + 250 and 500 ALOF), and cotreatment with SIL and ALOF (DEN + SIL + 250 and 500 ALOF). At the end of the study, the serum levels of liver indices (albumin, total protein, bilirubin, C-reactive protein, ALT, AST, and ALP), inflammatory cytokines (IL-6, IL-1β, IL-10, and TNF-α), and oxidants parameters (glutathione peroxidase [GPx], superoxide dismutase [SOD], catalase [CAT] activity along with nitric oxide [NO] levels) were evaluated. The level of Bax, Bcl-2, Caspase-3, p53, PI3K, mTOR, and AKT genes were measured. ALOF in cotreatment with SIL was able to regulate liver biochemical parameters, improve serum antioxidant indices, and decrease the level of proinflammatory cytokines significantly (p < .05). ALOF extract in both doses of 250 and 500 mg/kg in cotreatment with SIL caused a significant (p < .05) decrease in the p53-positive cells and a significant (p < .05) increase in Bcl-2-positive cells. Therefore, ALOF was able to modulate the proliferation of cancer cells and protect normal cells through the regulation of Bax/Bcl-2/p53 and PI3K/Akt/mTOR signaling pathways. It seems that ALOF can be used as a prodrug or complementary treatment in the protection of hepatocytes in induced damages caused by carcinogens.