## 1 Introduction  
Liver toxicity mediated by drug metabolism is the most serious problem [1, 2]. In the body, the principal organ involved in drug and xenobiotics metabolism is the liver [3, 4]. Although most of the drugs at therapeutic dose are usually metabolized by the liver without causing liver injury, over-administration of drugs can be a point of concern for liver toxicity [5, 6, 7]. The ability of the liver to metabolize xenobiotics (toxins) is interrupted when the harmful entities enter the bloodstream at a more rapid frequency than its capability to process them. The damage to the liver is frequently caused by drug-prompted toxicity. Acetaminophen (paracetamol) is a popular analgesic and antipyretic medication that is widely used. The metabolic pathway for acetaminophen involves three main phases including glucuronidation, sulfation, and cytochrome P450 2E1 oxidation. The mechanism of acetaminophen metabolism involves sulfate conjugation and glucuronidation resulting in the production of inert metabolites, usually expelled in the urine in sulfate and glucuronide conjugate form [8]. Consumption of paracetamol in overdoses generates reactive intermediates or metabolites in the liver, which causes disruption of cellular biomolecules leading to hepatic toxicity [9; 10]. It has been assumed that the most important factors that facilitate acetaminophen-induced liver injury involve the generation of free radicals (ROS) [11], nitric oxides, peroxides [12], and transcription factor NF-kB [13]. However, depending on dose, usually at a higher dose of acetaminophen, glutathione content in the body is depleted and a fraction of acetaminophen is metabolized to a highly toxic byproduct (N-acetyl-p-benzoquinone imine, NAPQI) by cytochrome P450 2E1 (CYP2E1). NAPQI has the potential to covalently bind to cellular molecules, thereby causing disruption of nuclear and mitochondrial functions, resulting in generation of ROS and RNS by hepatic non-parenchymal cells and infiltration of phagocytes causing centrilobular necrosis in the liver [14]. Moreover, depletion of glutathione leads to the inhibition/reduction in the biotransformation of NAPQI to mercapturic acid, which is a harmless excretable water-soluble product. Thus, any strategy that results in restoring the glutathione levels will ameliorate the acetaminophen-induced liver toxicity. In addition to oxidative damage, various transcription factors, NF-kB, and activator protein-1 (AP-1) participate in signal transduction pathways [6]. These are known to modulate inflammatory mediating genes including TNF-\(\alpha\), COX-2, nitric oxide synthase II, and IL-1\(\beta\), which are all involved in acetaminophen-induced hepatotoxicity [15]. Medicinal plants have been widely used for therapeutic purposes with relatively less knowledge about their mode of action. Therefore, evaluation of pharmacological activities of medicinal plants has becoming a growing field of research. Several drugs from natural sources are known to protect the free radical-induced organ damage. _Carum carvi_ L. is a well-known herb, traditionally used as spice and medicinally as a carminative, for gastrointestinal complaints, for lack of appetite, and in relieving infant flatulent folic disease [16]. Moreover, aqueous extract of _Carum carvi_ has been used as an aphrodisiac, aperitif, diuretic, tranquilizer, gastric stimulant, antiulcerogenic, antitumor, antiproliferative, antihyperglycemic, and antimicrobial [17]. On the basis of these considerations and available literature, the current study aimed to evaluate the role of _Carum carvi_ in the amelioration of hepatotoxicity induced by acetaminophen and elucidating its role in modulating the NF-kB, TNF-\(\alpha\), glutathione content, and caspases expression in rat models.