Effect of fenugreek (Trigonella foenum graecum L.) ethanolic extract on carbon tetrachloride-induced hepatotoxicity in rats

Background and Purpose: The liver performs various pivotal functions, including protein synthesis, glucose homeostasis, detoxification, and the utilization of various nutrients. Generally, when the liver is exposed to high levels of environmental toxins, metabolic dysfunction of the liver may occur, which ranges from the transient elevation of liver enzymes to life‐threatening hepatic fibrosis, liver cirrhosis, and even hepatocellular carcinoma. Substantial evidence implicates oxidative stress and inflammation in the aetiology of liver injury. Similar effects are caused by carbon tetrachloride (CCl4), an industrial solvent known to induce liver injury and liver diseases, which is widely used in experimental hepatopathy. CCl4‐induced toxicity depends on the dose and duration of exposure. At a low dose, transient effects occur, including the loss of Ca2+ sequestration, impaired lipid homeostasis, and the release of several cytokines. Longer exposures alter fatty acid metabolism and induce fibrosis, cirrhosis, and cancer. CCl4‐induced hepatotoxicity is the result of reductive dehalogenation reactions catalyzed by the hepatic cytochrome P‐450, which forms unstable trichloromethyl and trichloromethyl peroxyl radicals capable of binding to proteins or lipids and initiating lipid peroxidation and liver damage. Oxidative stress has been accepted as one of the principal causes of CCl4‐induced hepatic injury, which is mediated by the production of free radical derivatives of CCl4 and is responsible for cell membrane damage and the subsequent release of the marker enzymes of hepatotoxicity. Inflammation is another important pathological mechanism through which CCl4‐induced liver injury is propagated. Plants have a long history of medicinal applications across cultures, and many modern pharmaceuticals were originally derived from botanicals. Fenugreek (Trigonella foenum graecum L.) is an annual legume crop widely cultivated in Asia, Africa and the Mediterranean countries where it is often used for the edible and medicinal values of its seeds. In other countries like Canada and England, fenugreek is used for incorporation into short-term crop rotation due to its high adaptability to dry climatic conditions, annual nature, and ability to fix atmospheric nitrogen in the soil. As a feed for livestock, it is regarded as a bloat-free crop that contains growth-promoting compounds such as steroids and diosgenin, which are not present in other forage legumes. Fenugreek is a plant whose seeds have been historically used in cooking and as a herbal remedy, with anti-microbial, anti-inflammatory, anti-oxidant, anti-cancer, and anti-diabetic effects. Current research on fenugreek, most carried for therapeutic purposes, has shown that it contains beneficial chemical constituents including steroidal sapogenins, fibre, galactomannans, antioxidants, and amino acids such as 4-hydroxy isoleucine which possess antidiabetic, antioxidative, hypocholesterolemic, hypoglycemic, anti-inflammatory, antiulcerogenic, antitumor and immunomodulatory properties. To evaluate fenugreek as a hepatoprotective agent, we investigated the protective effect of fenugreek seed extract against CCl4-induced hepatic toxicity in rats. Materials and Methods: A total of 48 male Wistar rats were randomly divided into eight groups. The normal control group was intact. The liver-injured group was received CCl4 (1 ml/kg bw, 50%, i.p.) twice a week for 10 times. Normal experimental groups received fenugreek extract (50, 100 and 200 mg/kg bw, intragastrically). Liver-injured experimental groups administrated fenugreek extract (3 doses as above) along with CCl4. The rats were sacrificed on the 34th day, and blood was withdrawn by cardiac puncture. At the end of the 34-day treatment, the rats were fasted for 12 h and killed under mild (diethyl ether) anaesthesia. Blood was immediately obtained after the animals were sacrificed. The blood was withdrawn by cardiac puncture, allowed to clot and the serum was separated by centrifuging. The level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamaglutamyltransferase (GGT) were measured. Data were analyzed using one-way ANOVA and Tukey test. The criterion was significant (p

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