Hypobaric hypoxia induced renal injury in rats: Prophylactic amelioration by quercetin supplementation

Abstract

The present study aims at assessing the effect of hypobaric hypoxia induced renal damage and associated renal functions in male SD rats. Further, this study was extended to explore the protective efficacy of quercetin in ameliorating the functional impairment in kidneys of rats under hypobaric hypoxia. Rats were exposed to 7620m (25000 ft.) at 25°C ±2 in a simulated hypobaric hypoxia chamber for different time durations (0h,1h, 3h, 6h, 12h, 24h and 48h) in order to optimize the time at which maximum renal damage would occur. The rats were exposed to hypoxia for 12h duration was considered as the optimum time, due to significant increase in oxidative stress (ROS, MDA) and renal metabolites (creatinine, BUN and uric acid) with remarkable reduction (p<0.001) in antioxidants (GSH) in plasma, as compared to other tested durations. Moreover, these findings were in support with the histopathology analysis of renal tissues. For optimum quercetin dose selection, the rats were administered with different doses of quercetin (25mg, 50mg, 100mg and 200mg/Kg BW) for 12h at 7620 m, 25°C ±2, 1h prior to hypoxia exposure. Quercetin 50mg/kg BW was considered as the optimum dose at which significant (p<0.001) reduction in oxidative stress levels followed by reduction in creatinine and BUN levels were obtained in plasma of the rats compared to hypoxia control rats. Quercetin prophylaxis (50mg/kg BW) stabilized the HIF-1α protein expression followed by reduced VEGF protein expression along with reduced levels of LDH (p<0.001) in the kidneys of rats compared to hypoxia control. Histopathological observations further substantiated these findings in reducing the renal tissue injury. The study findings revealed that, quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced renal injury by reducing the oxidative stress in rats.

Dimethyl sulfoxide as a gas phase charge-reducing agent for the determination of PEGylated proteins' intact mass

“…The mass range for the PEG chain in PEG-lgrastim was calculated to be between 19 807.6 Da (448 EO units) to 22 891.4 Da (518 EO units), which correlates well with the ∼20 kDa PEG used during PEGylation of lgrastim of molecular weight 18 798.8 Da. 33,34 This also demonstrates that the method is capable of accurately distinguishing between variable PEG chain lengths. The intact mass analysis results for six preparations show that the post-column DMSO infusion method provides a high degree of reproducibility and accuracy.…”

“…It has been widely characterized for the development of biosimilars, and the use of LC-MS for the characterization of intact mass has been reported by such companies. [33][34][35] However, the exact methodology remains unclear. Therefore, the method presented here was applied to eight different Neulasta® lots to determine the intact molecular weight.…”

Quercetin prophylaxis protects the kidneys by modulating the renin–angiotensin–aldosterone axis under acute hypobaric hypoxic stress

“…Drugs quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) were freshly prepared by dissolving into a vehicle i.e., 0.5% DMSO and supplemented orally to Sprague Dawley (SD) rats 1 h prior to the hypobaric hypoxia exposure. Quercetin 50 mg/Kg BW dose was opted, based on the dose standardization studies carried out in our laboratory 26 . Dosage of acetazolamide was given on the basis of the previous literature 27 .…”

“…Glutathione reductase (GSH) followed by improved renal function parameters i.e. creatinine, Blood Urea Nitrogen (BUN) and uric acid under hypoxic stress among other tested doses 26 .…”

“…The rats were exposed to hypobaric hypoxia in a simulated hypoxia chamber (Matrix, India) for 12 h at an altitude of 25,000 ft. (7620 m). Standardization of time duration was performed in our previous experiments which showed that, 12 h duration (among the tested durations 1 h, 3 h, 6 h, 12 h, 24 h and 48 h) of hypoxia exposure was the optimum time, at which maximum renal damage had occurred 26 . Internal hypobaric hypoxia chamber pressure was maintained at (280 mm Hg) with fresh air flushing at the rate of 4 lit/h along with the relative humidity of 55 ± 5%.…”