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.

Amelioration of immune and digestive system through weed supplemented feed against Aeromonas hydrophila in Clarias gariepinus.

Aquaculture is one of the important globally growing industries. It serves as an important food source of protein for human beings. With the expanding demand for the fish and their products it has become extremely important to improve the aquaculture practices. Aquaculture in India has witnessed huge mortalities caused by bacteria, viruses, fungi, nematodes etc. Aquatic weeds plants are harmful for aquaculture in many ways. Present study is aimed to overcome the disease caused by Aeromonas hydrophila (fish pathogenic bacteria) through feed supplementation of two aquatic weed plants (Azolla pinnata and Ceratophyllum demersum). The fish were divided into 6 groups: experimental groups (fish fed on supplementary feed at 5% and 2.5% concentration for individual plant and challenged with bacteria), positive control (fish fed on non-supplemented feed and challenged with bacteria) and negative control (fish fed on non-supplementary feed and not challenged with bacteria). It was observed that supplemented feed enhanced both cell mediated and humoral immunity in fish. Therefore, we advocate that feed formulated with incorporation of Azolla pinnata and Ceratophyllum demersum leaf powder at 5% and 2.5% could be used to prevent disease caused by A. hydrophila or can be used to enhance fish health by boosting its immune system. The results of this study also showed an improved digestibility in fish fed on supplemented feed.

Association of Monoamine Oxidase A with Tumor Burden and Castration Resistance in Prostate Cancer.

BACKGROUND: Metastatic burden and aggressive behavior determine severity stratification and guide treatment decisions in prostate cancer (PCa). Monoamine oxidase A (MAOA) may promote tumor burden and drug/castration resistance in PCa. A positive association will pave the way for MAOA inhibitors such as moclobemide for PCa therapy. OBJECTIVE: To analyze MAOA in peripheral blood mononuclear cells qualitatively and p38, c-Jun N-terminal kinases, nuclear factor kappa B, and their phosphorylated forms, vascular endothelial growth factor (angiogenesis), transforming growth factor beta, interleukin 6, and tumor necrosis factor-α (cytokines), Bcl-2 associated X, B-cell lymphoma 2, and P53 (apoptosis), prostate-specific membrane antigen, and epithelial cell adhesion molecules (surface markers) in plasma of patients with PCa. METHODS: This was a 1-year pilot study in which patients with PCa were recruited and stratified into 2 groups and subgroups: treatment-naive with (M1) (n = 23) or without (M0) (n = 23) bone metastasis; hormone-sensitive prostate cancer (n = 26) or hormone/castration-resistant prostate cancer (n = 26). MAOA was detected using ELISA and other proteins were detected using immunoblotting technique. RESULTS: MAOA was detected in 8.6% of M0 compared with 30.4% of M1 patients, and in 7.7% of hormone-sensitive compared with 27% of hormone/castration resistant PCa patients, associating it with bone metastasis and castration resistance. Multivariable regression analysis showed a correlation of MAOA with serum prostate-specific antigen, a marker for progression in PCa (Pearson correlation coefficient r = 0.30; P < 0.01). In patients with positive MAOA, there was overexpression of p38, phosphorylated-p38, c-Jun N-terminal kinases, phosphorylated c-Jun N-terminal kinases, nuclear factor kappa B, phosphorylated nuclear factor kappa B, transforming growth factor beta, vascular endothelial growth factor, interleukin 6, tumor necrosis factor α, Bcl-2 associated X, B-cell lymphoma 2, prostate-specific membrane antigen, and epithelial cell adhesion molecule in M1 compared with M0 group patients, associating these proteins with tumor burden. Overexpression of Bcl-2 associated X, tumor protein 53, c-Jun N-terminal kinases, nuclear factor kappa B, transforming growth factor beta, vascular endothelial growth factor, and prostate-specific membrane antigen and underexpression of B-cell lymphoma 2 and phosphorylated nuclear factor kappa B were observed in hormone-sensitive prostate cancer compared with hormone/castration-resistant prostate cancer, associating these proteins with castration resistance. CONCLUSIONS: Association of key molecules of oncogenesis and metastasis with MAOA suggests that MAOA inhibitors such as moclobemide might be effective in the management of PCa.

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.

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.

Hesperidin regresses cardiac hypertrophy by virtue of PPAR-γ agonistic, anti-inflammatory, antiapoptotic, and antioxidant properties.

Hesperidin (HES), a flavanone glycoside, predominant in citrus fruits, has an agonistic activity on peroxisome proliferator-activated receptor gamma (PPAR-γ). PPAR-γ is an inhibitor of cardiac hypertrophy (CH) signaling pathways. In this study, we investigated the cardioprotective effect of HES in isoproterenol (ISO)-induced CH through PPAR-γ agonistic activity. For this, male albino Wistar rats were divided into six groups (n = 6), that is, normal, ISO-control, HES treatment group (200 mg kg-1 ; p.o.), HES per se (200 mg kg-1 ; p.o.), enalapril treatment group (30 mg kg-1 ; p.o.), and combination group (HES 200 mg kg-1 ; p.o.+enalapril 30 mg kg-1 ; p.o.). ISO (3 mg kg-1 ; s.c.) was administered to all groups except normal and per se to induce CH. HES or enalapril treatment of 28 days significantly attenuated pathological changes, improved cardiac hemodynamics, suppressed oxidative stress, and apoptosis along with an increased PPAR-γ expression. The combination of enalapril with HES exhibited an effect similar to that of HES or enalapril alone on all the aforementioned parameters. Therefore, HES may be further evaluated as a promising molecule for the alleviation of CH.

Leucaena leucocephala pod seed protein as an alternate to animal protein in fish feed and evaluation of its role to fight against infection caused by Vibrio harveyi and Pseudomonas aeruginosa.

The laboratory acclimatized Clarias gariepinus (80 ±â€¯10 g) were divided into six groups and five subgroups each containing 10 fish. A fish feed was reconstituted by adding 33% powder of Leucaena leucocephala seed in place of fish trash. Group B, C and E were fed on reconstituted feed and group A, D and F were fed on artificial feed containing animal protein for 7 days prior to start of experiments. Then Group B was challenged with BSA while other groups were challenged with Vibrio harveyi (Group C, D) and Pseudomonas aeruginosa (Group E, F). Group A was used as negative control (not challenged with antigen). The fish were challenged on weekly intervals till 28th day. Blood was collected from one subgroup of each group on day 7, 14, 21 & 28 and finally sacrificed on day 35. Change in body weight, liver function tests (SGOT, SGPT) and serum ALP levels were monitored. The phagocytic index, percentage phagocytosis and nitric oxide levels were measured in macrophages isolated from spleen and head kidney. The levels of total fish immunoglobulin were also measured following indirect ELISA. The results showed improved immune response in fish fed on 33% L. leucocephala pod seed reconstituted feed; however their specific growth rate was low.

Flavonoids as therapeutics for myocardial ischemia-reperfusion injury: a comprehensive review on preclinical studies.

Ischemic heart disease is the most prevalent cause of death worldwide affecting both the gender of all age groups. The high mortality rate is due to damage of myocardial tissue that emanates at the time of myocardial ischemia and re-oxygenation, thus averting reperfusion injury is recognized as a potential way to reduce acute cardiac injury and subsequent mortality. Flavonoids are polyphenol derivatives of plant origin and empirical shreds of evidence substantiate their numerous activities such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-thrombotic activity, leading to their role in cardio protection. Recent investigations have unveiled the capacity of flavonoids to impede pivotal regulatory enzymes, signaling molecules, and transcription factors that orchestrate the mediators participating in the inflammatory cascade. The present comprehensive review, dwells on the preclinical studies on the effectiveness of flavonoids from the year 2007 to 2023, for the prevention and therapeutics for myocardial ischemia-reperfusion injury.

Therapeutic potential of Ficus benghalensis in thromboembolic disorders.

Ficus benghalensis L. (FB) is a popular plant described in the Indian system of medicine. Traditionally, it is indicated in the treatment of diseases like diabetes mellitus, dysentery, leucorrhoea, menorrhagia, skin disease, rheumatism, inflammatory diseases, blood disorders. This paper accentuates the anti-thrombotic action of FB based on the properties like anti-coagulant, platelet-antiaggregatory, anti-atherogenic hypotensive, hypolipidemic, anti-oxidant, anti-inflammatory and immunomodulatory. All the available data pertaining to FB has been searched in the scientific databases, including PubMed, Google Scholar, ScienceDirect and Scopus. FB is a rich lode of organic compounds such as phenols, flavonoids, alkaloids, tannins, terpenoids and steroids. The various studies show that these phytochemical constituents exhibit wide range of anti-thrombotic actions such as anticoagulant, platelet anti-aggregatory, anti-atherogenic, hypolipidemic, hypotensive, anti-inflammatory, and antioxidant. Various studies (in vitro and in vivo) confirm the potential anti-thrombotic benefit of FB due to the presence of chemical structures that have proven to be effective in thromboembolic conditions. These evidences may benefit in new drug development to treat varied thromboembolic conditions which will not only be cost effective but may allay the fear of side effects.

Arglabin: A mediator of inflammasome modulated and independent myocardial injury (PARA-AMI study).

BACKGROUND: Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects. PURPOSE: Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium. STUDY DESIGN: This study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 µg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups. METHODS: On the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin. RESULTS: Arglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose. CONCLUSION: Arglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.

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.

Abatacept: A Promising Repurposed Solution for Myocardial Infarction-Induced Inflammation in Rat Models.

Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant-antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.

Immunostimulatory effect of artificial feed supplemented with indigenous plants on Clarias gariepinus against Aeromonas hydrophila.

The antibacterial activity of methanol extracts of Ficus benghalensis (prop-root) and Leucaena leucocephala (pod seed) was evaluated by measurement of zone of inhibition against pathogenic bacteria, Escherichia coli and Aeromonas hydrophila. Control artificial feed and artificial feed supplemented with 5% powder of F. benghalensis and L. leucocephala were prepared. Juvenile Clarias gariepinus were divided into four groups, acclimatized to laboratory conditions and fed with respective feeds for 20 days prior to the experiment. Immunomodulatory response of supplementary feed was studied by challenging the fish intraperitoneally at weekly intervals, with A. hydrophila. One set of fish, not challenged with A. hydrophila was used as a negative control, to analyze any detrimental effect of supplementary feed, while positive control, comprised of challenged fish fed with non-supplemented feed. Other two groups of fish were challenged with A. hydrophila and fed with respective supplementary feeds. Blood was collected on weekly intervals for four weeks and serum samples were analyzed to evaluate the damage of fish by A. hydrophila through liver function tests. The increase in the levels of Serum glutamic oxaloacetic transaminase (SGOT) and Serum Glutamic pyruvate transaminase (SGPT) in positive control group indicated the damage of liver & kidney. However the levels did not change significantly in fish fed with supplementary feeds when compared to negative control group. Nitric oxide, SOD, ALP and lipid peroxidase indicated lower stress levels in these fish compared to positive control. Fish fed with supplementary feed showed increased lysozyme activity and phagocytic index indicating an increase in non-specific immune response. The immunoglobulin levels of in serum were analyzed by homologous sandwich ELISA, which showed higher antibody production in fish fed with supplementary feed. The current study suggests conclusively, immunostimulatory role of F. benghalensis (prop-roots) and L. leucocephala (pod seed) in C. gariepinus when supplemented in artificial feed.

In-silico Assessment of Polyherbal Oils as Anti-diabetic Therapeutics.

BACKGROUND: Diabetes mellitus (DM) is characterized by elevated blood glucose levels either due to insufficient insulin production, defective insulin action, or both. It affects nearly 537 million individuals worldwide. Pharmacological treatment involves the use of oral antidiabetic agents as mono or combination therapy that effectively aids in controlling hyperglycemia. Despite providing therapeutic benefits, these medications limit their use owing to adverse side effects. Certain natural products, including essential oils, have promising anti-diabetic properties. OBJECTIVE: The present study explores the effectiveness of two polyherbal oils and their compound towards the treatment of DM based on an In-silico approach to drug investigations. METHODS: Compounds present in the polyherbal oil formulation were identified using GCMS/MS analysis. Selected compounds undergo molecular docking with the receptor, and proteins play an important role in DM. The potential compounds showing higher interactions than the known inhibitors or inducers were evaluated using molecular dynamic simulations RMSD values. RESULTS: The compounds identified through GC-MS analysis possess anti-diabetic and antiinflammatory properties. With the aid of in silico prediction methods, compounds such as geraniol, cinnamaldehyde, anethole, caryophyllene, terpinyl acetate, cymene, linalool, menthol, Phenol,2-methoxy-3-(2-propenyl), and 2,6- octadienal,3,7-dimethyl were identified as strong binders of GLUT4 and insulin receptor proteins. Geraniol and Phenol,2-methoxy-3-(2-propenyl) interaction with GLUT4 were of particular importance owing to their conformational stability. CONCLUSION: Our data suggest an agonistic effect of compounds on target proteins aiding in enhanced insulin activity and could serve as a potential anti-diabetic agent.

Immunostimulatory response induced by supplementation of Ficus benghalensis root powder, in the artificial feed the Indian freshwater murrel, Channa punctatus.

Methanol extract from the dried aerial root of Ficus benghalensis, was used to evaluate antibacterial activity on the bacterial strains of Aeromonas hydrophila and Escherichia coli, by disc diffusion method. In order to study, if there is any immunostimulatory response of F. benghalensis, immunized fish were fed with supplementary artificial feed containing 5% F. benghalensis dried root powder. There was no marked difference in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in control and treated fish, suggesting that the supplementary feed had no adverse effect on liver or kidney. Serum lysozyme, tissue super oxide dismutase (SOD), percentage phagocytosis, phagocytotic index, nitric oxide (NO), total serum protein and immunoglobulin increased significantly in the treated fish compared to control fish. Serum immunoglobulin levels were estimated by development of a sandwich ELISA, and levels were found to increase with successive immunizations of BSA.

Integrating in silico and in vivo approach for investigating the role of polyherbal oil in prevention and treatment of COVID-19 infection.

Currently, there are no FDA approved antiviral drugs available to treat COVID-19 patients. Also, due to emergence of new SARS-CoV-2 variants, the protective efficacy of vaccines could be reduced, hence it is urgent to have alternative treatments for combating the SARS-CoV-2 infection. Since, there is a long-standing history of herbal medicine in the treatment of respiratory diseases. In the present study, we investigated two polyherbal oil blend viz. Sudarshan AV and Elixir AV (SAV and EAV) in inhibiting SARS-COV-2. From GC-MS analysis of polyherbal oils (SAV and EAV) a total of 11 active compounds were selected, on the basis of their abundance and activity. Further, from the molecular docking studies, we found an inhibitory effect of these compounds on viral envelope and membrane, spike proteins whilst an agonistic effect with human host receptor angiotensin-converting enzyme 2 (ACE2) implicating the crucial role of the individual compound in resistance of SARS-CoV-2. Since, the in-silico results suggest that polyherbal oil (SAV and EAV) contributes in preventing the entry of SARS-CoV-2 into the human body, we further investigated the efficacy of polyherbal formulated essential oil (FEO; SAV & EAV) in prevention and treatment of COVID-19 in hamster model. The male golden Syrian hamsters (n = 23) were divided into 5 groups i.e., Group 1: Control (n = 3); Group 2: Infected (n = 5); Group 3: Infected + Remdesivir (n = 5); Group 4: Infected + FEO (n = 5) and Group 5: Prophylactic FEO + Infected (n = 5). In both treatment and prophylactic groups, the FEO's significantly reduced the lung injury investigated histo-pathologically and viral load expression measured by real time PCR in comparison to infected hamsters. Furthermore, cytokines expression analysis clearly highlighted the efficacy of FEO's due to its anti-inflammatory activity and overall protection in treatment groups. In conclusion, the FEO (SAV & EAV) seem to be potent in both prevention and treatment of COVID-19 and related lung injury.

Correlation of serum amyloid A1 and interleukin-1beta in response to anti-tubercular therapy.

BACKGROUND: Host biomarkers are needed to monitor the response to anti-tubercular therapy (ATT) for ensuring effective therapy and preventing drug-resistant tuberculosis. We sought to find the correlation between the serum levels of SAA1 and IL-1beta in response to ATT in adult patients with pulmonary TB (PTB) or extra-pulmonary TB (EPTB). METHODS: Blood samples of 32 patients with PTB and 28 patients with EPTB were analyzed. The blood samples were collected at baseline, two months and six months following treatment initiation. SAA1 and IL-1beta levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: In the PTB group, the mean levels of SAA1 decreased significantly (p <0.001) after the intensive phase (two months) and continuous phase (six months) of ATT in comparison with the baseline value. IL-1beta values also decreased significantly (p = 0.005) after the intensive phase (two months) compared with the baseline values. In the EPTB group, there was a significant reduction in the mean serum level of SAA1 (p <0.001) and IL-1beta (p = 0.001) after the intensive phase (two months) in comparison with the baseline value, whereas the reduction at six months was not significant. CONCLUSIONS: SAA1 and IL-1beta may be useful potential treatment-monitoring biomarkers, especially in the intensive phase of therapy for both PTB and EPTB.

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.

Study of genetic polymorphism in solvent exposed population and its correlation to in vitro effect of trichloroethylene on lymphocytes.

Trichloroethylene (TCE) is major industrial pollutant that contaminate environment. Its exposure may lead to hepato-renal toxicity along with the cancer progression. Although extensive research is done on its toxicity still not much is known about its genotoxic potential on humans in relation to genetic polymorphism. Cytochrome P450 (CYP P-450) and glutathione-S-transferases (GSTs) are important in cellular detoxification of TCE. Variations in gene sequences result in population specific regional genetic variations (polymorphism). Genotyping of CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphism was performed in 220 normal and 97 solvent-exposed individuals from northern part of India using real time PCR, PCR and restriction digestion techniques. The parameters examined to study genotoxicity were chromosomal aberration (CA) and cytokinesis block micronucleus assay (CBMN) in lymphocyte culture in vitro. The observed average frequencies for GSTM1 (null) and GSTT1 (null) were 41, 22 and 12.7%, respectively in normal subjects whereas frequencies of CYP1A1/GSTP1 with (ile/ile) or (ile/val) or(val/val) were found to be 76.2/52, 21.4/42.1 and 2.4/5.9% respectively. It was further observed that the frequencies of above genes were found to be similar in solvent exposed groups. The distribution frequencies of GST genes, when compared with other reports from various regions of India show variations. In vitro TCE exposure (2, 4 and or 6 mM) did not show any significant genotoxic effect. TCE maybe toxic due to its metabolite.