Elumalai Balamurugan

Lithium Modulates Biochemical Circadian Rhythms in Wistar Rats

We studied the effects of chronic lithium treatment on circadian rhythms of glucose, cholesterol, calcium, potassium, malondialdehyde (MDA), and lactic acid in Wistar rats. Lithium altered the peak time, range, and 24h mean of these biochemical rhythms. Peak times of the circadian rhythms of glucose, calcium, and potassium were delayed by 3h, 6h, and 6h, respectively, whereas circadian rhythms of MDA and lactic acid were advanced by 9h and 3h, respectively, in lithium-treated rats. Delays observed in our experiments would support the hypothesis that lithiums therapeutic effect is to delay overtly fast circadian rhythms. Advances of peak times owing to lithium treatment are discussed.

Molecular metabolic fingerprinting approach to investigate the effects of borneol on metabolic alterations in the liver of nitric oxide deficient hypertensive rats

Hypertension is one of the major risk factor that underlie a wide range of cardiovascular irregularities which causes functional and metabolic alterations in vascular system and major organs. Nitric oxide is the central regulator of the vascular system and its deficiency leads to increased blood pressure and metabolic alterations in liver. Fourier transform infrared spectroscopy (FTIR) is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds with in the sample that absorbs it and different samples contain diverse configurations of molecular bonds. Both wavenumber and area of the vibrational spectra can be used to explore the qualitative and quantitative constituent of macromolecules. In this study, we intended to evaluate the protective role of borneol, a natural terpene on liver metabolism in a nitric oxide deficient model of hypertension through interpretation of FTIR spectral information. Results demonstrate that FTIR can successfully indicate the molecular changes that occur in all groups. The over all findings demonstrate that in nitric oxide deficient animal model of hypertension, the liver metabolic program is altered through increasing the structural modification in proteins and triglycerides, and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected by borneol in liver and showed its ability to exert a novel defensive action on hepatic metabolism.

Diosgenin interferes coronary vasoconstriction and inhibits osteochondrogenic transdifferentiation of aortic VSMC in CRF rats.

Cardiovascular dysfunction and vascular calcification is the leading cause of death in chronic renal failure (CRF) patients. This study was designed to evaluate the effect of diosgenin on coronary flow resistance and to address the question whether the previously proven antivascular calcification potential of diosgenin is associated or not with the osteochondrogenic transdifferentiation of vascular smooth muscle cells (VSMC). In this study, CRF in Wistar rats was induced by fed with 0.75% adenine and diosgenin was treated everyday at the dose of 40 mg/kg. Langendorff based isolated heart protocol was employed to analyze the coronary flow resistance. Western blot method was used to explore the phosphorylation dynamics of endothelial nitric oxide synthase (eNOS) at the serine 1177 residue. In addition, cardiac nitric oxide metabolites level also assessed. Quantitative expression of VSMC and osteochondrogenic markers was also evaluated. Antioxidant potential of diosgenin was studied in vitro. The outcome of the present study explores that diosgenin treatment significantly improves the coronary resistance and increased the nitric oxide metabolites level compared with CRF. Further, diosgenin increases the phosphorylation of eNOS (peNOS ser1177). Moreover, diosgenin reduced the aortic expression of osteochondrogenic markers and improved the VSMC phenotype components. Further, diosgenin shows concentration dependent antioxidant potential. In conclusion, this study have proven that diosgenin have enough potential to improve the coronary function and interfere the osteochondrogenic transdifferentiation program of aortic VSMC which supports its antivascular calcification potential.

Temporal oscillations of serum electrolytes in N-phthaloyl GABA-treated rats

N-Phthaloyl gamma-aminobutyric acid (P-GABA) has been known to cross the blood-brain barrier and ultimately to increase brain GABA level. In the present study, P-GABA was administered to Wistar rats for 21 days and circadian rhythms of sodium, potassium, and calcium levels in serum were studied under seminatural light-dark conditions. P-GABA administration caused desynchronization of the rhythms and advanced the peak times of serum electrolytes. Exogenously administered P-GABA could alter the photic information received by the clock. The results could be explained by slightly less or more than 1-h daily delays, which would bring the peak times to the points 21 days after the start of administration. The changes in amount of electrolytes after P-GABA administration are discussed.

Diosgenin, a steroidal saponin, prevents hypertension, cardiac remodeling and oxidative stress in adenine induced chronic renal failure rats

Patients with chronic renal failure (CRF) are at a high risk of developing cardiovascular diseases. The aim of the present study was to evaluate the effect of diosgenin on blood pressure, cardiac remodeling, contractile function and gene expression program in the context of oxidative stress in CRF rats. CRF was induced in rats by feeding them with 0.75% adenine-containing diet, and diosgenin was given orally everyday at the dose of 10, 20 and 40 mg kg−1 body weight of animal. The effect of diosgenin on systolic blood pressure (SBP), activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), angiotensin converting enzyme (ACE) activity and lipid peroxidation level in heart were evaluated. Cardiac function (dp/dt) and percentage rate pressure product (%RPP) recovery after ischemia/reperfusion (I/R) were evaluated by Langendorff isolated heart system, and gene expression levels were assessed by real-time PCR. Fibrotic remodeling of heart was assessed by histopathologic analyses. The outcome of this study demonstrated that a dose dependent treatment with diosgenin reduces hypertension in CRF animals, and a 40 mg kg−1 dosage exhibited more pronounced effect on the blood pressure. Diosgenin enhances the antioxidant level, attenuates ACE activity, lipid peroxidation level and cardiac fibrosis. Ventricular function and %RPP recovery after I/R were also improved by the diosgenin treatment. CRF induced expression of transforming growth factor-β (TGF-β) and β-myosin heavy chain (β-MHC) were also suppressed by diosgenin. Taken together, these results suggest that diosgenin have enough potential to attenuate cardiac remodeling by reducing blood pressure and oxidative stress in the heart of CRF rats.

Diosgenin prevents hepatic oxidative stress, lipid peroxidation and molecular alterations in chronic renal failure rats

Aim: Chronic renal failure (CRF) is one of the major contributors of cardiovascular pathological events and CRF associated uremic condition in rats elevates liver oxidative stress. The aim of the present study was to evaluate the preventive potential of diosgenin on antioxidant system and molecular protection potential in liver of CRF rats. Materials and Methods: CRF in rats was induced by feeding rats with diet containing 0.75% adenine for 5 weeks. Diosgenin was given orally at a dose of 40 mg/kg body weight (bw) of animal each and every day. The activities of antioxidant enzymes and lipid peroxidation level were determined by biochemical assays. Fourier transform infrared spectroscopy (FTIR) was employed to illustrate the molecular protection potential of diosgenin. Results: This study has shown adenine containing diet induced CRF in rats elevates liver oxidative stress by suppressing the activity of enzymatic antioxidant system, increased lipid peroxidation, and macromolecular structural alterations. In this study, treatment of diosgenin 40 mg/kg bw of rat significantly restores the enzymatic antioxidant system and reduces the lipid peroxidation level. Moreover, based on the FTIR study, we confirmed that diosgenin administration significantly protected the macromolecular changes including, the protein structural damage that occurred in liver. Conclusion: This study has proved the hepato protective action of diosgenin through antioxidant and molecular protection effect in CRF condition.