Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice

BACKGROUND: Nitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen consumption, nitric oxide (NO) synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice. RESULTS: Hyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS) levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice. CONCLUSIONS: These findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.

Effects of low concentrations of a polychlorinated biphenyl, Aroclor 1254 on membrane bound ion dependent ATPases in mice liver.

Aroclor 1254, a polychlorinated biphenyl, is present in the environment in low concentration but references on its toxic effects on liver cell membrane proteins and the mechanism of actions are not abundantly available. Therefore, the present study was undertaken to investigate the low level, sub-acute dose and exposure duration dependent effects of Aroclor 1254 on total, Na+, K+, Ca2+ and Mg2+-ATPases of the mouse liver. The hypotheses tested in the present study were, (a) whether the low, environmentally available dose and the exposure durations of Aroclor 1254 affects the membrane-bound ion dependent ATPases, and (b) if a response was observed, whether it is a direct or indirect effects of the toxicant. Groups of mice were exposed to different doses (0.1 and 1mg kg-1 body weight d-1) and exposure durations (4 d, 8 d and 12 d) of Aroclor 1254. The results indicated significant exposure duration dependent changes in the specific activity of the selected membrane bound ATPases. As the observed changes were mostly enzyme stimulation after toxication through oral administration, the effects of the Aroclor were possibly indirect, through complex chain of reactions.

Acute exposure to lead increases myocardial contractility independent of hypertension development

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

Estimation of efflux mediated multi-drug resistance and its correlation with expression levels of two major efflux pumps in mycobacteria.

Multidrug resistance has been posing an increasing problem in the treatment of tuberculosis. Mutations in the genomic targets of drugs have been identified as the major mechanism behind this resistance. However, high degree of resistance in some isolates towards major drugs like rifampicin, isoniazid, ethambutol and streptomycin can not be explained solely on the basis of mutations. Besides this, certain other mechanisms like efflux pumps have also been considered as alternative mechanisms in the drug resistant isolates where there is no mutation and these mechanisms are specially important for drug resistance in non-tuberculous mycobacteria (NTM). In this study, we have estimated efflux pump mediated drug resistance in different mycobacterial species with the help of efflux pump inhibitors. All major anti-tuberculous drugs have been shown to be extruded by efflux pumps and the degree to which these drugs are extruded, vary in different mycobacterial species and isolates. The correlation of this resistance with functional activity of two major efflux pump genes pstB and Rv1258c was also assessed by reverse transcription PCR. Besides the significant role of these pumps observed, other efflux pumps, present in mycobacteria, may also be involved in drug resistance and need to be investigated.

Influence of gentamicin on the ATPase, electrolytes lipid peroxides and histology of rat renal cortical tissues

Calcium, magnesium, sodium and potassium dependent ATPases and their corresponding cations together with the lipid peroxides and proteins were determined in renal cortical homogenate of five groups of adult male albino rats [6 animals each] from which one group was used as control and the other 4 groups were treated with a low dose of gentamicin [10 mg/-kg/D] for up to 21 days. The activity levels of the Na[+], K[+] ATPases were significantly inhibited after 15 days of treatment compared to the control whereas Mg[2]+, Ca[2]+ ATPases activity showed nonsignificant change from the control values. Both sodium and calcium cations concentrations significantly increased after 15 days in contrast to potassium and magnesium cations levels which showed a significant decrease after 15 days of treatment compared to the control values. In addition, rat renal cortical homogenates showed a significant increase in lipid peroxide levels throughout the first 15 days of gentamicin treatment. These findings were associated with histological and histochemical changes. It can be concluded that biochemical changes in renal tissue reflect the possible cellular damage. However, these changes were reversed and levels were returned to normal after 21 days of gentatmicin treatment. Therefore gentamicin should be used very cautiously using the lowest possible therapeutic dose and if it is necessary to use it, its nephrotoxic effect should be monitored in aged or critically-ill patients to detect the early laboratory and functional changes