Morin ameliorates myocardial injury in diabetic rats via modulation of inflammatory pathways.

BACKGROUND: High blood glucose levels in diabetes lead to vascular inflammation which accelerates atherosclerosis. Herein, Morin was orally administered in male Wistar rats, at the dose of 40 mg/kg for 28 days, and on the 27th and 28th day, ISO was administered to designate groups at the dose of 85 mg/kg s.c., to induce myocardial infarction. RESULTS: Free radical generation, including ROS, in diabetes following ISO administration, leads to the activation of both intrinsic and extrinsic pathways of apoptosis. Morin significantly (p ≤ 0.05) reduced oxidative stress (GSH, MDA, SOD), cardiac injury markers (CK-MB, LDH), inflammation (TNF, IL-6), and apoptosis (Bax, BCl2, Caspase-3). In addition, it also reduced insulin and blood glucose levels. Akt/eNOS, Nrf2/HO-1, MAPK signaling pathways, and Insulin signal transduction pathways were positively modulated by morin pre-treatment. CONCLUSIONS: Morin attenuated oxidative stress and inflammation and also modified the activity of various molecular pathways to mitigate cardiomyocyte damage during ISO-induced MI in diabetic rats.

Galangin ameliorates cisplatin induced nephrotoxicity in vivo by modulation of oxidative stress, apoptosis and inflammation through interplay of MAPK signaling cascade.

BACKGROUND AND PURPOSE: Cisplatin is a widely used chemotherapeutic agent but now-a-days its usage is limited in clinical chemotherapy because of its severe nephrotoxic effect on renal tissues. Galangin, a flavonoid obtained from ginger family has been demonstrated to have antioxidant, anti-apoptotic and anti-inflammatory properties. This study is aimed to investigate the possible ameliorative effect of galangin in a rodent model of cisplatin-induced nephrotoxicity. MATERIAL AND METHODS: Adult male albino wistar rats were divided into six groups (n=6) viz normal, cisplatin-control, galangin (25, 50 and 100mg/kg p.o.) and per se (100mg/kg galangin, p.o.). Galangin was administrated orally to the rats for a period of 10 days. On the 7th day of the treatment, nephrotoxicity was induced in all the groups by a single dose of cisplatin (8mg/kg, i.p.) (except normal and per se group). On the 11th day, the rats were anaesthetized and blood was withdrawn via direct heart puncture for biochemical estimation. Rats were sacrificed and kidneys were isolated and preserved for evaluation of histopathological, ultra structural immunohistochemical studies and western blot analysis. RESULTS: Cisplatin significantly impaired renal function and increased oxidative stress and inflammation. It also increased expression of pro-apoptotic proteins Bax and caspase-3 and decreased the expression of the anti-apoptotic protein Bcl-2. Histological and ultrastructural findings were also supportive of renal tubular damage. Pretreatment with galangin (100mg/kg p.o.) preserved renal function, morphology, suppressed oxidative stress, inflammation and the activation of apoptotic pathways. TUNEL assay showed decreased DNA fragmentation on galangin pre-treatment. Furthermore, galangin (100mg/kg) pre-treatment also reduced the expression of NFκB along with proteins MAPK pathway i.e. p38, JNK and ERK1/2. CONCLUSION: In conclusion, Galangin (100mg/kg, p.o.) significantly ameliorated cisplatin induced nephrotoxicity by suppressing MAPK induced inflammation and apoptosis.

Role of oxidative stress markers and antioxidants in the placenta of preeclamptic patients.

AIM: The present study aimed to evaluate and compare the placental variables of oxidative stress markers in preeclamptic women. METHODS: A total of 60 placentas were collected. Of these, 30 were obtained from normotensive pregnancies, and 30 from pregnancies with preeclampsia as per International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Each placental tissue was analyzed for levels of pro-oxidant (malondialdehyde) and antioxidants (glutathione and superoxide dismutase) using the standard enzymatic assays. RESULTS: Malondialdehyde levels were significantly higher (12.21 ± 4.1 versus 4.7 ± 2.1 nmol/g tissue, P < 0.0001) and glutathione (GSH) levels were significantly lower (0.46 ± 0.37 versus 1.03 ± 0.43 µmol/g tissue, P < 0.0001) in the placentas of preeclamptic women when compared to those of normal pregnancies. Though not statistically significant, decreases in superoxide dismutase levels were observed in placentas of preeclamptic women (4.14 ± 2.25 versus 5.22 ± 2.0 units/mg tissue protein, P < 0.055). Receiver operator characteristic curve analysis of malondialdehyde revealed a sensitivity of 87% and specificity of 87%, at a cutoff value 6.5 nmol/g. Similarly, GSH had a sensitivity of 77% and a specificity of 77% at a cutoff value 0.62 µmol/g. CONCLUSION: The present study demonstrated that increased placental lipid peroxidation and decreased levels of antioxidants may play an important role in the pathogenesis of preeclampsia. These findings are suggestive of involvement of oxidative stress markers in preeclamptic patients.