crocin and Necrosis

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 was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L. (Saffron) against subchronic diazinon (DZN) induced cardiotoxicity in rats.. Rats were divided into 7 groups; control (corn oil, gavage), DZN (15 mg/kg/day, gavage,), crocin (12.5, 25 or 50 mg/kg/day, i.p) plus DZN, vitamin E (200 IU/kg, i.p, three times per week) plus DZN and crocin (50 mg/kg/day, i.p) groups. Treatments were continued for 4 weeks. Creatine phosphokinase MB (CK-MB), malondealdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. Levels of apoptotic proteins (Bax, Bcl2, caspase 3) and cytosolic cytochrome c were analyzed by Western blotting. Transcript levels of Bax and Bcl2 were also determined using qRT PCR.. DZN induced histophatological damages and elevated the level of cardiac marker CK-MB. These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax/Bcl2 ratio (both protein and mRNA levels), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue. Crocin (25 and 50 mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. In summary, DZN induced mitochondrial-mediated apoptosis in heart tissue of rat following subchronic exposure. Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Carotenoids; Creatine Kinase; Crocus; Cytochromes c; Diazinon; Disease Models, Animal; Gene Expression; Glutathione; Heart; Heart Diseases; Insecticides; Male; Malondialdehyde; Myocardium; Necrosis; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; RNA, Messenger

Among various naturally occurring compounds which have been extracted from Crocus sativus, crocin has shown different pharmacological effects i.e. neuroprotection and anti-tumor activity.. Here, crocin effects on human T-cell leukemia cell line, MOLT-4, were evaluated. In this study, we examined the effects of 24 and 48 h of crocin treatment (50, 250 and 500 µM) on the viability of MOLT-4 cell line. Moreover, probable apoptotic/necrotic outcomes, reactive oxygen species (ROS) production variations along with crocin treatment consequences on DNA, were investigated.. Results from MTT assay demonstrated that 48-h crocin treatment at 500 µM, significantly reduced cell viability (p<0.01). DNA fragmentation was recorded to be significantly increased at higher doses of crocin following 24 and 48 h (p<0.01). According to our results, while apoptosis was detected at all concentrations, necrosis detected at the highest dose, only. In comparison with control, ROS production was reduced at 50 and 250 µM.. In accordance with previous reports, crocin exhibited mild cytotoxic effects on a leukemia cell line which might be mediated through the increase of DNA fragmentation.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carotenoids; Cell Line, Tumor; Cell Survival; Crocus; DNA Fragmentation; Humans; Leukemia; Necrosis; Phytotherapy; Plant Extracts; Reactive Oxygen Species

We used an experimental model in the rat to examine the effects of long-term treatment with crocin, a glycosylated carotenoid from the stigmas of the saffron crocus, on colon cancer. BD-IX rats were divided into four groups: Groups G1 and G2, designated "cancer groups," were used to study the effects of crocin on the progression of colon cancer, and Groups G3 and G4, designated "toxicity groups," were used to study the effects of the treatment on metabolic processes and the parenchyma. DHD/K12-PROb cells were injected subcutaneously into the chest of Group G1 and G2 animals. From 1 to 13 weeks after inoculation, animals in Groups G2 and G4 received a weekly injection of crocin (400 mg/kg body wt s.c.). Animals in Groups G1 and G3 received no treatment. In addition, lines of animal and human colon adenocarcinoma cells (DHD/K12-PROb and HT-29) were used to perform assays in vitro to examine the cytotoxicity of crocin. Life span was extended and tumor growth was slower in crocin-treated female rats, but no significant antitumor effect was found in male rats. Acute tubular necrosis was found in all kidney samples from crocin-treated animals, but slight signs of nephrotoxicity were found by biochemical analysis of the serum. In assays in vitro, crocin had a potent cytotoxic effect on human and animal adenocarcinoma cells (HT-29 and DHD/K12-PROb cells, 50% lethal dose = 0.4 and 1.0 mM, respectively). Treated cells exhibited a remarkable loss of cytoplasm and wide cytoplasmic vacuole-like areas. In conclusion, long-term treatment with crocin enhances survival selectively in female rats with colon cancer without major toxic effects. The effects of crocin might be related to its strong cytotoxic effect on cultured tumor cells.

Topics: Adenocarcinoma; Animals; Carotenoids; Cell Survival; Colonic Neoplasms; Female; Humans; Kidney Diseases; Kidney Tubules; Liliaceae; Male; Necrosis; Neoplasm Transplantation; Rats; Tumor Cells, Cultured