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.

Evidence-based mechanistic role of chrysin towards protection of cardiac hypertrophy and fibrosis in rats.

Cardiac hypertrophy is the enlargement of cardiomyocytes in response to persistent release of catecholamine which further leads to cardiac fibrosis. Chrysin, flavonoid from honey, is well known for its multifarious properties like antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic. To investigate the cardioprotective potential of chrysin against isoproterenol (ISO), cardiac hypertrophy and fibrosis are induced in rats. Acclimatised male albino Wistar rats were divided into seven groups (n 6): normal (carboxymethyl cellulose at 0·5 % p.o.; as vehicle), hypertrophy control (ISO 3 mg/kg, s.c.), CHY15 + H, CHY30 + H & CHY60 + H (chrysin; p.o.15, 30 and 60 mg/kg respectively + ISO at 3 mg/kg, s.c.), CHY60 (chrysin 60 mg/kg in per se) and LST + H (losartan 10 mg/kg p.o. + ISO 3 mg/kg, s.c.) were treated for 28 d. After the dosing schedule on day 29, haemodynamic parameters were recorded, after that blood and heart were excised for biochemical, histological, ultra-structural and molecular evaluations. ISO administration significantly increases heart weight:body weight ratio, pro-oxidants, inflammatory and cardiac injury markers. Further, histopathological, ultra-structural and molecular studies confirmed deteriorative changes due to ISO administration. Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways. Data demonstrated that chrysin attenuated myocardial hypertrophy and prevented fibrosis via activation of transforming growth factor-beta (TGF-ß)/Smad signalling pathway.

Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf-2/HO-1 pathway.

Isoproterenol (ISO) induced oxidative stress and inflammation is involved in the pathogenesis of myocardial necrosis. To optimize the effect of erdosteine against myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6), that is, normal, ISO-control, erdosteine pretreatment with ISO. Rats were administered erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to ISO-C and erdosteine treatment groups on the 27th and 28th day. On the 29th day, hemodynamic parameters were recorded and the heart was excised for further parameters. In ISO-C rats, significantly increased levels of inflammatory markers, pro-oxidants, and structural damage were observed as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed an increased expression of apoptotic proteins. Erdosteine at 80 mg/kg reversed the deleterious effects of ISO and normalized myocardium. Erdosteine showed anti-inflammatory, antiapoptotic, and antioxidant activities through inhibition of MAPK and Nrf-2/HO-1 pathways. To conclude, erdosteine was found protective in ISO-induced myocardial necrosis through MAPK and Nrf-2/HO-1 pathway.

Frequency and predictors of compliance among patients taking antihypertensive medicines.

INTRODUCTION: Medication compliance, an important aspect in the treatment of chronic disease research, is often assessed using pill count method. The patient perception is usually not addressed objectively. The present study was conducted to assess patient cognizance, prevalence and predictors of compliance towards antihypertensive therapy in Indian patients. METHODS: Adult patients taking antihypertensive medicines were included from the cardiology and geriatric OPDs of a tertiary care hospital in India. Socio-demographic data and disease awareness information was collected. Hill-Bone high blood pressure compliance scale was administered for compliance score. RESULTS: For the 452 participants, mean age was 54.6 ± 13.7 years with approximate 2:1 ratio of males to females. Cronbach's alpha value of 0.7 for Hill Bone compliance scale showed good internal consistency. More than 80% participants had a score of ≥80%, showing good compliance among Indian patients. Factors that were significantly associated with uncontrolled blood pressure with correlation analysis were age, gender and awareness regarding disease. CONCLUSION: The study suggests that Hill-Bone high blood pressure compliance scale may be useful for assessing compliance in Indian population. An age appropriate intervention for continued compliance should be considered to improve compliance and hence, reduce long term sequelae of hypertension.

Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity.

BACKGROUND: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models. AIM: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism. METHODS: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters. RESULTS: As compared to cisplatin-control group, Ber pretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin mediated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney. CONCLUSION: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/ PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.

Attenuation of ROS-mediated myocardial ischemia-reperfusion injury by morin via regulation of RISK/SAPK pathways.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of myocardial ischemia-reperfusion (IR) injury. Morin, a bioflavonoid, has demonstrated antioxidant, anti-inflammatory and other diverse pharmacological activities in various experimental models such as isoproterenol-induced myocardial injury, doxorubicin-induced cardiotoxicity and neurotoxicity, as well as cisplatin-induced nephrotoxicity. Thus, this study aimed to evaluate the effect of morin in myocardial IR injury model and its underlying mechanisms. METHOD: To accomplish this, male albino Wistar rats were pre-treated with morin (40 and 80 mg/kg; po) for 28 days and on 29th day, rats experienced 45-min myocardial ischemia followed by 60-min reperfusion. RESULTS: In comparison to IR-control group, morin pre-treatment significantly normalized hemodynamic parameters, restored antioxidant status, improved pathological changes, reduced the release of cardiac injury markers, inhibited inflammation (TNF-α/IL-6/NFκB/IKKß) and apoptosis (increased Bcl-2, decreased Bax/Caspase-3 and TUNEL positivity) in the myocardium. This improvement in antioxidant, inflammation and anti-apoptosis markers could be due to downregulation of SAPK (p38/JNK) pathway and upregulation of survival kinase, i.e. RISK pathway (ERK/eNOS) in the myocardium. CONCLUSION: Thus, morin attenuated myocardial IR injury in rats by regulation of RISK/SAPK pathways.

Role of MAPK/NF-κB pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats.

Oxidative stress plays a major role in myocardial injury. Morin, a bioflavonoid has known to possess various biological activities in previous studies. Hence, this study evaluated the cardioprotective mechanism(s) of Morin against isoproterenol induced myocardial necrosis in rats. Male albino Wistar rats were divided into five groups (n = 8) i.e., I (normal), II (ISO-control), III, IV and V (morin 20, 40 and 80 mg/kg respectively). Groups III, IV and V were treated orally with daily doses of Morin accordingly for 28 days. On 26th and 27th day, a single injection of isoproterenol was injected (85 mg/kg s.c.) at 24 h interval to induce myocardial necrosis in group II, III, IV and V. On 28th day, hemodynamic parameters were evaluated, animals were euthanised and heart was excised for measurement of various parameters. In ISO-control rats, there was deterioration of hemodynamic parameters, decreased anti-oxidants levels, increased cardiac injury markers and pro-inflammatory cytokines (TNF-α and IL-6). Also, there was increased level of Bax, Caspase-3, p-JNK, p-38 and NF-κB and decreased expression of Bcl-2 and p-ERK1/2 in ISO-C group. Morin dose-dependently improved hemodynamic profile, increased anti-oxidant levels, normalized myocardial architecture and reduced inflammatory markers and apoptosis. Furthermore, immunoblot analysis of MAPK pathway proteins demonstrated the mechanism responsible for anti-apoptotic and anti-inflammatory potential of morin. Thus, this study substantiated the beneficial effect of Morin by virtue of its modulation of MAPK pathway in myocardial injury.

Mangiferin attenuates cisplatin-induced acute kidney injury in rats mediating modulation of MAPK pathway.

Cisplatin has been confined due to the reported cases of nephrotoxicity. In the present study, an active xanthone, Mangiferin (from Mangifera indica) was investigated for its defensive role in cisplatin-induced nephrotoxicity. Male wistar albino rats were divided into six groups i.e., group 1 (normal); group 2 (cisplatin control); group 3, 4, and 5 (mangiferin 10, 20, and 40 mg/kg, i.p.); and per se (40 mg/kg; i.p.). The treatment was given for 10 days. On day 7, single dose of cisplatin 8 mg/kg i.p. was administered to induce nephrotoxicity in all groups except normal and per se. On day 11, animals were anesthetized, blood was taken from heart and serum was separated. Thereafter, rats were sacrificed and kidneys were isolated and preserved for histopathological, ultrastructural, immunohistochemical, and western blot analysis. Cisplatin control group showed significant impairment in renal function due to increased inflammation and oxidative stress which was also confirmed by histopathology and MAPK pathway proteins expression. However, pretreatment with mangiferin 20 and 40 mg/kg significantly reversed the renal function along with the structural changes and the levels of antioxidants. Mangiferin treatment attenuated DNA damage and apoptotic pathway.

Influence of Qualification and Practice Settings of Dental Practitioners on Antimicrobial Prescribing in Delhi and National Capital Region, India.

BACKGROUND AND OBJECTIVES: Inappropriate antimicrobial prescribing is highly reported in dentistry. The objective of the study was to see the effect of dental qualification and practice settings on antimicrobial prescribing practices among dental practitioners in Delhi and National Capital Region (NCR) of India. MATERIALS AND METHODS: A self-designed and pretested questionnaire was given to 667 dental practitioners holding degrees of graduation, postgraduation, and those pursuing postgraduation, working in academic institutions and private clinics in NCR of India. Data were analyzed using statistical software Stata version 12.0. Chi-square and logistic regression tests were used for analysis. RESULTS: Out of total 539 responded, 66.4% of the practitioners prescribed by brand name and 27.8% by generic name. Amoxicillin + clavulanic acid (27.4%) was the first choice. Only 26% of the practitioners asked for antimicrobial susceptibility testing. Space infections (91.9%), impacted third molar extractions (89.7%), and periodontal abscess (88.1%) were the conditions where antimicrobials were most frequently prescribed. However, 60.9% and 53.3% of the practitioners also prescribed antimicrobials for acute pulpitis and dry socket, respectively. For prophylaxis in medical conditions, amoxicillin was the first choice. In case of history of allergy to penicillin, 52.3% of the practitioners prescribe erythromycin whereas 14.6% prescribe amoxicillin. The adverse drug reporting culture was negligible, and only 14.3% of the practitioners were aware of the Pharmacovigilance Program of India. Level of qualification had a significant effect on prescribing (P < 0.05). INTERPRETATION AND CONCLUSION: Frequent irrational prescribing of antimicrobials used in odontogenic conditions warrants an urgent and continued need for guidelines as well as educational intervention programs in dentistry. This will improve the quality of antimicrobial prescribing practices in dentistry.