Reactive oxygen species (ROS) play a key role in the pathophysiological processes of renal diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of ROS in the stationary state (oxidative stress). Oxidative stress mediates a wide range of renal impairments, from acute renal failure, rhabdomyolysis, obstructive nephropathy, hyperlipidemia, and glomerular damage to chronic renal failure and hemodialysis. Therefore, interventions favoring the scavenging and/or depuration of ROS (dietary and pharmacological antioxidants) should attenuate or prevent the oxidative stress, thereby mitigating against the subsequent renal damage.
There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of carvedilol (CVD), an antihypertensive drug in I/R-induced renal failure in rats. The protective effect of CVD against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments, animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Carvedilol (2 mg/kg, i.p.) was administered twice, 30 min prior to ischemia and 12 h after the reperfusion period. At the end of the reperfusion period, rats were killed. Thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with CVD markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R-induced renal injury and CVD exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
Summary
Canine distemper (CD) is one of the highly contagious and invariably fatal viral diseases of dogs and other carnivores. Despite the widespread use of modified live vaccines to control CD, the prevalence of disease has increased at an alarming rate in recent years. Although a number of factors may be ascribed for vaccine failure, antigenic differences among the vaccine and wild‐type strains have gained the interest of researchers. Considering the high genetic variability of haemagglutinin gene (H gene) and its role in eliciting the immune response to canine distemper virus (CDV), we have generated nine full‐length CDV H gene sequences from infected dogs including three vaccinated cases. Bayesian analysis was performed using 102 full‐length H gene nucleotide sequences over a time frame of 76 years (1940–2016) from 18 countries. The time to the most recent common ancestor (tMRCA) of CDV was estimated to be 1696 AD. Phylogenetic reconstruction clustered Indian wild‐type viruses into a distinct monophyletic group clearly separated from the previously established CDV lineages. This signifies the presence of a novel genetic variant (proposed as “Lineage India‐1/Asia‐5”) circulating among dog population in India. To investigate the importance of substitutions at amino acid residues 530 and 549 of CDV H protein in determining the host switches from canid to non‐canid hosts, we analysed 125 H gene sequences including nine sequences generated in this study. Selection pressure analysis and analysis of amino acid sequences revealed a trend towards adaptation of 549H variants in non‐canid hosts although no role of G/E530R/D/N substitution could be identified. This is the first comprehensive study about the nature and ecology of CDV circulating among dog population in India. Outbreaks in vaccinated animals as observed in this study have raised a concern towards the effectiveness of current vaccine strains warranting detailed investigation.
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