Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl₄)–Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation

Abstract

Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical-generating CYP2E1 enzyme.

Profile of bioactive compounds in Nymphaea alba L. leaves growing in Egypt: hepatoprotective, antioxidant and anti-inflammatory activity

“…In the present study caspase-3 was extensively expressed in the liver excised from CCl 4 -intoxicated rats denoting the correlation between CCl 4 induced hepatotoxicity and the high level of apoptosis of the hepatocytes as previously reported [50]. N. alba decreased the level of caspase-3 expression while the effect of the high dose of N. alba is similar to that of silymarin as both drugs showed negative staining for caspase-3.…”

Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway

“…2, PRO group: rats were treated with PRO (400 mg/kg, i.g.) for 15 consecutive days . 3, CIS group: rats were treated with normal saline, i.g.…”

Hepatoprotective effect of phenylethanoid glycosides from Incarvillea compacta against CCl4-induced cytotoxicity in HepG2 cells

“…oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) into serum and eventually kills cells (Dai et al 2014;Yu et al 2011). Therefore, antioxidative property is claimed to be one of the mechanisms of hepatoprotective effect (Bhardwaj et al 2011).…”