Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver. The aim of this study is to evaluate the comparative in silico and in vivo ameliorative potential of the ethanolic extract of Curcuma longa (EECL) in male and female Wistar rats administered N-nitrosodiethylamine-induced hepatocellular carcinoma. The MAPK compound was obtained from a protein data bank (PDB ID: 7AUV) for molecular docking. One hundred and twenty Wistar rats, were randomly selected into twelve groups (n = 5): Group A received regular diets as a basal control; groups B to G were administered 100 mg/kg NDEA twice in two weeks; while groups C to E received 200 mg/kg, 400 mg/kg, and 600 mg/kg of EECL; group F was treated with 200 mg/kg pure curcumin; and group G received 100 mg/kg Sylibon-140. Group H received only 200 mg/kg pure curcumin, and group I received 200 mg/kg of dimethylsulfoxide (DMSO). Groups J, K, and L received 200 mg/kg, 400 mg/kg and 600 mg/kg of EECL. MAPK and AFP mRNA in Wistar rats administered NDEA were upregulated as compared to EECL groups. In conclusion, the in silico and in vitro study validates the mitigating role of ethanolic extract of Curcuma longa and pure curcumin.

Organisms frequently suffer negative effects from large doses of ionizing radiation. However, radiation is not as hazardous at lower doses as was once believed. The current study aims to evaluate the possible radio-adaptive effect induced by low-dose radiation (LDR) in modulating high-dose radiation (HDR) and N-nitrosodiethylamine (NDEA)-induced lung injury in male albino rats. Sixty-four male rats were randomly divided into four groups: Group 1 (control): normal rats; Group 2 (D): rats given NDEA in drinking water; Group 3 (DR): rats administered with NDEA then exposed to fractionated HDR; and Group 4 (DRL): rats administered with NDEA then exposed to LDR + HDR. In the next stage, malondialdehyde (MDA), glutathione reduced (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in the lung tissues were measured. Furthermore, the enzyme-linked immunoassay analysis technique was performed to assess the Toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 4 (IRAK4), and mitogen-activated protein kinases (MAPK) expression levels. Histopathological and DNA fragmentation analyses in lung tissue, in addition to hematological and apoptosis analyses of the blood samples, were also conducted. Results demonstrated a significant increase in antioxidant defense and a reduction in MDA levels were observed in LDR-treated animals compared to the D and DR groups. Additionally, exposure to LDR decreased TLR4, IRAK4, and MAPK levels, decreased apoptosis, and restored all the alterations in the histopathological, hematological parameters, and DNA fragmentation, indicating its protective effects on the lung when compared with untreated rats. Taken together, LDR shows protective action against the negative effects of subsequent HDR and NDEA. This impact may be attributable to the adaptive response induced by LDR, which decreases DNA damage in lung tissue and activates the antioxidative, antiapoptotic, and anti-inflammatory systems in the affected animals, enabling them to withstand the following HDR exposure.

Targeting mitochondrial oxidative stress during initial stages of hepatocarcinogenesis can be an effective and promising strategy to prevent hepatocellular carcinoma (HCC). In the present study, mitochondria targeted antioxidant, mito-TEMPO was administered to male BALB/c mice at a dosage 0.1 mg/kg b.w. (intraperitoneal) twice a week, followed by single N-Nitrosodiethylamine (NDEA) intraperitoneal injection (10 mg/kg b.w.). After 24 h of NDEA administration, animals were sacrificed, blood and liver tissue were collected. Liver injury markers, histoarchitecture, antioxidant defence status, mitochondrial reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial dysfunction analysis, and mitochondrial membrane potential were investigated. Mito-TEMPO pre-treatment protected animals from the damaging effects of NDEA as observed by normalization of liver injury markers. NDEA metabolism resulted in a significantly increased intracellular and mitochondrial ROS generation with concomitant increase in LPO formation. The activity of mitochondrial complex I, complex II, malate dehydrogenase were significantly reduced and mitochondrial membrane potential was increased. Mito-TEMPO effectively scavenged NDEA-induced ROS generation and reduced LPO formation. A significant improvement was also observed in the activity of mitochondrial complex I, complex II, malate dehydrogenase and normalisation of mitochondrial membrane potential. Results suggested that mito-TEMPO had significant impact on the initiation phase of hepatocarcinogensis which could be one of the reason for its reported chemopreventive effect.