crocin and Chemical-and-Drug-Induced-Liver-Injury

Doxorubicin (DXR) is widely used in cancer treatment. However, it has not yet been possible to prevent the side effects of DXR. The aim of this study was to investigate the hepatoprotective effect of crocin against DXR used in cancer treatment. For this reason; forty Wistar rats (male-250-300 g) were allocated into four groups (n = 10/group): Control, Crocin, DXR and DXR+Crocin. Control and Crocin groups were administered saline and crocin (40 mg/kg, i.p) for 15 days, respectively. DXR group, cumulative dose 12 mg/kg DXR, was administered for 12 days via 48 h intervals in six injections (2 mg/kg each, i.p). DXR+Crocin group, crocin (40 mg/kg-i.p) was administered for 15 days, and DXR was given as in the DXR group. The results revealed that serum liver markers (alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) increased significantly after DXR administration but recovered after crocin therapy. In addition, lipid peroxidation (MDA), and inflammatory cytokine (TNF-α) increased after DXR application and the antioxidative defense system (GSH, SOD, CAT) significantly decreased and re-achieved by crocin treatment. Our results conclude that crocin treatment was related to ameliorated hepatocellular architecture and reduced hepatic oxidative stress and inflammation in rats with DXR-induced hepatotoxicity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury; Doxorubicin; Liver; Male; Oxidative Stress; Rats; Rats, Wistar

Leflunomide-induced liver injury has been an important problem since its approval. Although, severe cases of leflunomide-induced liver injury leading to hospitalization are rare, the risk is higher with concurrent liver disease or use of other hepatotoxic drugs. The current study was conducted to investigate the potential protective effects of carvedilol and crocin alone and in combination against leflunomide-induced hepatic injury and to clarify the possible mechanism(s) through which carvedilol and crocin may elicit their effects. Fifty male albino mice were allocated into five groups: normal control group, leflunomide group, carvedilol group, crocin group, and combination group. These groups were given vehicle, leflunomide, leflunomide plus carvedilol, leflunomide plus crocin, and leflunomide plus combination of carvedilol and crocin, respectively. The study was conducted for 8 weeks, and different parameters were assessed. The results demonstrated that leflunomide significantly increased the serum levels of AST, ALT, ALP, hepatic MDA, nitrite, mTOR gene, PI3K gene, TGF-β, and the pathological changes alongside with the significant decrease of serum albumin, total protein, hepatic catalase, and GSH. While the coadministration of carvedilol, crocin and their combination with leflunomide significantly decreased the serum levels of AST, ALT, ALP, hepatic MDA, mTOR gene, PI3K gene, TGF-β, and the pathological changes alongside with the significant elevation of serum albumin, total protein, hepatic catalase, and GSH. This study is suggesting several solutions for Leflunomide-induced hepatotoxicity demonstrated by the protective effect of the antihypertensive drug carvedilol, the natural product crocin, and their combination which was demonstrated to be superior to each drug alone.

Topics: Animals; Carvedilol; Catalase; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Leflunomide; Liver; Male; Mice; Oxidative Stress; Phosphatidylinositol 3-Kinases; Serum Albumin; TOR Serine-Threonine Kinases; Transforming Growth Factor beta

The objective of the present study was to demonstrate the protective effect of crocin on the adverse effects of tartrazine on liver. Crocin is a carotenoid and a strong free radical scavenger. Forty rats were randomly divided into 4 groups (n = 10). The first group was the control group (C) and saline solution was administered to this group. The second group (Cr) was administered 50 mg/kg crocin. The third group (T) was administered 500 mg/kg tartrazine. The fourth group (T+Cr) was administered the same doses of both crocin and tartrazine as the previous groups for 21 days. It was determined that tartrazine increased liver superoxide dismutase (SOD) activity, malondialdehyde (MDA) and total oxidant status (TOS) levels and catalase (CAT) activity, decreased glutathione (GSH), and total antioxidant status (TAS) levels. Furthermore, tartrazine administration resulted in significant increases in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and pathological changes in the liver. When tartrazine administered rats were treated with crocin for 21 days, the biochemical parameters improved, and liver tissues were restored. Thus, it was demonstrated that crocin had protective effects on the adverse effects caused by tartrazine administration.

Topics: Animals; Antioxidants; Biomarkers; Carotenoids; Chemical and Drug Induced Liver Injury; Food Coloring Agents; Liver; Oxidative Stress; Random Allocation; Rats; Tartrazine

Diazinon (DZN) is one of the most widely used insecticides in agricultural pest control. Previous studies have shown that DZN may induce hepatotoxicity. Reactive oxygen species and apoptosis pathways are involved in the toxicity of DZN. Crocin, a constituent of saffron, has hepatoprotective effects due to its antioxidant activity. In this study, we examined the effects of subacute DZN exposure and ameliorating effect of crocin on lipid peroxidation and pathological changes in rat liver. Moreover, protein levels of activated and total caspases-3 and -9 and Bax/Bcl-2 ratio were measured. Five groups of rats were used in the experiment. Corn oil (control), DZN (15 mg/kg per day, orally) and crocin (12.5, 25 and 50 mg/kg per day, intraperitoneally in combination with DZN) were given to male Wistar rats (n = 6) for 4 weeks. The level of malondialdehyde (MDA) increased significantly in DZN group compared with the control group (p < 0.05). MDA level decreased significantly in the group that received DZN plus 25 mg crocin (p < 0.001). No gross or histological evidence of treatment-related damage to the liver after oral exposure to DZN was observed. DZN also induced apoptosis through activation of caspases-9 and -3 and increasing Bax/Bcl-2 ratio. Crocin attenuated the activation of caspases and reduced the Bax/Bcl-2 ratio. It is concluded that subacute exposure to DZN induces oxidative stress-mediated apoptosis and crocin may reduce DZN-induced hepatotoxicity.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Carotenoids; Caspases; Chemical and Drug Induced Liver Injury; Cholinesterase Inhibitors; Diazinon; Insecticides; Lipid Peroxidation; Liver; Male; Protective Agents; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar

Cisplatin (CDDP) is one of the most frequently used antitumor agents, but its application is significantly limited by its hepatotoxicity. In the present study, we investigated the effects of crocin against CDDP-induced oxidative stress and apoptosis in the liver of Kunming mice. Crocin was administered to the mice once daily for 7 consecutive days at the doses of 6.25 and 12.5 mg/kg body weight orally. On day 1, a single intraperitoneal injection of CDDP was given at the dose of 10 mg/kg body weight. Crocin treatment significantly improved CDDP-induced hepatic damage as indicated by serum aspartate aminotransferase and alanine aminotransferase levels. Crocin relieved CDDP-induced oxidative stress by reducing malondialdehyde level and recovering the levels of glutathione and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In addition, liver histopathology indicated that crocin alleviated CDDP-induced focal necrosis. Immunohistochemical staining and Western blot analysis showed that crocin significantly decreased the levels of phospho-p38 mitogen-activated protein kinase (MAPK), tumor protein 53 (p53), and cleaved caspase-3. Taken together, our data suggest that crocin provides protective effects against CDDP-induced hepatoxicity by attenuating oxidative stress and inhibiting the activation of p38 MAPK, p53, and caspase-3.

Topics: Animals; Antioxidants; Carotenoids; Caspase 3; Caspase Inhibitors; Chemical and Drug Induced Liver Injury; Cisplatin; Cytoprotection; Disease Models, Animal; Enzyme Activation; Liver; Mice; Necrosis; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Kinase Inhibitors; Signal Transduction; Tumor Suppressor Protein p53

This study investigated the protective efficacy of crocin against hepatotoxicity induced by cyclophosphamide (CP) in Wistar rats.. The experimental rats were treated with crocin orally at a dose of 10 mg/kg for 6 consecutive days after the administration of a single intraperitoneal dose of CP (150 mg/kg). The ameliorative effect of crocin on organ toxicity was studied by evaluating oxidative stress enzymes, inflammatory cytokines and histological sections.. A single intraperitoneal CP injection significantly elevated endogenous reactive oxygen species and oxidation of lipids and proteins, which are the hallmarks of oxidative damage in liver and serum. In consequence, the primary defensive reduced glutathione, total thiol and antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase, were significantly reduced. In addition, liver and serum aspartate aminotransferase and alanine aminotransferase along with acid and alkaline phosphatase were considerably increased. Oral administration of crocin significantly rejuvenated all the above altered markers to almost normal state. The protective efficacy of crocin was further supported by the histological assessment and restoration of CP-induced inflammatory cytokines and enzyme levels compared with the control drug.. The results obtained suggest the protective nature of crocin against CP-induced oxidative damage/inflammation and organ toxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Alkylating; Antioxidants; Biomarkers; Carotenoids; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Cytokines; Food Coloring Agents; Hydrogen Peroxide; Lipid Peroxidation; Liver; Oxidative Stress; Oxidoreductases; Protein Carbonylation; Protein Processing, Post-Translational; Rats; Rats, Wistar; Reactive Oxygen Species