Protective Effect of Crocin on Malathion-induced Cardiotoxicity in Rats: A Biochemical, Histopathological and Proteomics Study.

In this study, the protective effect of crocin on malathion (MTN) induced cardiotoxicity in rats in subacute exposure was evaluated. Rats were divided into 6 groups; control (normal saline); MTN (100 mg/kg); MTN + crocin (10, 20 and 40 mg/kg) and MTN + vitamin E 200 IU/kg. Treatments were continued for two weeks. Creatine phosphokinase MB (CK-MB), malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. The effect of crocin and MTN on histopathological changes in rat cardiac tissue was also investigated. The alteration of protein profile in the heart of the animals exposed to MTN was evaluated by proteomic approach through two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) software. MTN induced histopathological damages and elevated the level of cardiac marker CK-MB (P < 0.01). The level of MDA increased and the level of GSH reduced (P < 0.001). MDA levels were reduced in all crocin plus MTN groups (P < 0.001) and vitamin E plus MTN (P < 0.001) groups as compared to MTN groups. However, in the crocin (10 mg/kg) + MTN group, the content of GSH compared to MTN treated rats increased (P < 0.001). Protein abundance analysis identified proteins implicated in cardiac necrosis, tricarboxylic acid cycle, cellular energy homeostasis, arrhythmias, heart development, heart failure and cardiovascular homeostasis to be affected by MTN. In summary, MTN may induce damage in the heart tissue of rats following subacute exposure and crocin, as an antioxidant, showed protective effects against MTN cardiotoxicity.

Evaluation of epigallocatechin gallate and epicatechin gallate effects on acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells.

The neurotoxicity of acrylamide (ACR) monomer occurs through different mechanisms such as oxidative stress. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) are green tea catechins which are known as powerful antioxidants. In this study, we examined the possible protective effects of ECG and EGCG on ACR neurotoxicity in both in-vitro and in-vivo models. PC12 cells were exposed to different concentrations of ECG and EGCG. After 24 and 48 hours, ACR was added to the cells (IC50 = 4.85 mM) and cell viability was measured through MTT assay after 24 hours. Male Wistar rats were pretreated with ECG, EGCG (10, 20 and 40 mg/kg, i.p) and vitamin E (200 IU/kg i.p.) for 3 days. Afterwards they were treated with ACR (50 mg/kg, i.p.) for 11 days. After the treatment period, gait score examination was performed and molondialdehyde (MDA) and reduced glutathione (GSH) were measured in cerebral cortex. ACR reduced the cell viability in a concentration-dependent manner. Both ECG and EGCG (20 µM) showed inhibitory effects on ACR cytotoxicity. ACR significantly induced gait abnormalities, decreased GSH level and increased lipid peroxidation in cerebral cortex. ECG and EGCG (20 mg/kg) improved all ACR toxic effects. Although the food intake was increased in pretreated groups compared to the ACR-treated group, intensive weight loss was observed due to the green tea's different weight loss mechanisms. ECG and EGCG inhibited the cytotoxicity of ACR in PC12 cells and increased GSH level and decreased lipid peroxidation in rat cerebral cortex.

Study of the Role of CREB, BDNF, and VGF Neuropeptide in Long Term Antidepressant Activity of Crocin in the Rat Cerebellum.

Antidepressant activity of crocin, saffron main component, has been established before. Based on previous study, it is suggested that elevation in the levels of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide could be considered as one probable molecular mechanisms involved in antidepressant activity of long term crocin administration in the rat hippocampus. In this study we further investigated whether the antidepressant activity of crocin in long term administration was associated with alteration in these factors in the rat cerebellum. Crocin (12.5, 25 and 50 mg/kg/day) and imipramine (10 mg/kg/day) were administered interaperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were dissected. BDNF, VGF, CREB, and phospho-CREB (P-CREB) protein and mRNA levels in the rat cerebellum were evaluated using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the current study significant increases in mRNA and protein levels of VGF, CREB and (BDNF) in long term crocin treatment were not observed in the rat cerebellum. Although a slight increase was observed in protein level of P-CREB compared to normal saline, but it was not significant. It is concluded that antidepressant activity of crocin might be partially mediated to CREB. Moreover, other factors rather than BDNF and VGF neuropeptides may alter following long term crocin treatment in the cerebellum. To understand the precise mechanism of crocin antidepressant effects in the cerebellum, longer duration of crocin treatment in further studies is recommended.