Protective Effect of Daidzein against Diethylnitrosamine/Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Male Rats

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) claims the second-largest number of casualties among all forms of cancer. Several chemotherapeutic agents are being used for its treatment, but most have been discontinued because of their side effects or the development of resistance in the patients. Hence, exploring nutraceuticals is a way to manage this disease, citing greater efficacy and a lower degree of resistance development. Daidzein (DZ), a prominent isoflavone polyphenolic phytochemical found in leguminous plants, has tremendous pharmacological properties, including anti-inflammatory, antihemolytic, and antioxidant effects. The present investigation aimed to evaluate the protective effect of DZ in DEN/CCl4-induced HCC in a rat model. The dosing of DZ was initiated four weeks before HCC induction and continued until the end of the treatment period. In this study, four treatment groups of rats (n = 6) were designated as control (group 1, without any treatment), HCC-induced rats (group 2), an HCC group treated with DZ at 20 mg/kg (group 3), and an HCC group treated with DZ at 40 mg/kg (group 4). Group 2 rats showed marked elevation in all the HCC markers (AFP, GPC3, and VEGF), liver function markers (ALP, ALT, and AST), inflammatory markers (IL-6, TNF-α, and CRP), and lipid markers concomitant with a decrease in antioxidant enzymes and protein. Interestingly, groups III and IV demonstrated alleviation in most of the parameters of HCC in a dose-dependent way. Also, the histological alterations of HCC were significantly reduced in groups III and IV, confirming the results of biochemical analysis. Hence, DZ is a promising candidate for HCC treatment, attributed to its antioxidant and anti-inflammatory properties. ABSTRACT: Hepatocellular carcinoma (HCC) is the second-largest cause of death among all cancer types. Many drugs have been used to treat the disease for a long time but have been mostly discontinued because of their side effects or the development of resistance in the patients with HCC. The administration of DZ orally is a great focus to address the clinical crisis. Daidzein (DZ) is a prominent isoflavone polyphenolic chemical found in soybeans and other leguminous plants. It has various pharmacological effects, including anti-inflammatory, antihemolytic, and antioxidant. This present study investigates the protective effect of DZ on chemically induced HCC in rat models. The DZ was administered orally four weeks before HCC induction and continued during treatment. Our study included four treatment groups: control (group 1, without any treatment), HCC-induced rats (group II), an HCC group treated with DZ at 20 mg/kg (group III), and an HCC group treated with DZ at 40 mg/kg (group IV). HCC rats showed elevation in all the HCC markers (AFP, GPC3, and VEGF), liver function markers (ALP, ALT, and AST), inflammatory markers (IL-6, TNF-α, and CRP), and lipid markers concomitant with a decrease in antioxidant enzymes and protein. However, groups III and IV demonstrated dose-dependent alleviation in the previous parameters resulting from HCC. In addition, the high dose of DZ reduces many hepatological changes in HCC rats. All study parameters improved with DZ administration. Due to its antioxidant and anti-inflammatory characteristics, DZ is a promising HCC treatment option for clinical use.