Simulated vehicle exhaust exposure (SVEE) in rats impairs renal mitochondrial function

ABSTRACT

Purpose

 Vehicle exhaust emissions primarily comprise of nitrogen, oxygen, water, CO₂, NO₂, CO, hydrocarbons and particulate matter. While adverse effects of hydrocarbon and particulate matter on cardiovascular functions are known, the effect of pro-oxidants CO₂, NO₂ and CO are not clear.

Methods

 Here, using an animal model of a simulated mixture of pro-oxidants (0.04% CO₂, 0.9 ppm NO₂ and 3 ppm CO with air as a base), we examined the effect of simulated vehicle exhaust exposure (SVEE) on various cardiovascular parameters. Male Sprague-Dawley rats were exposed to SVEE or ambient air (Control: CON) for 30 min/day for 2 weeks. Thereafter, systolic and diastolic blood pressure, heart rate and glomerular filtration rate were measured. Later, rats were sacrificed, blood plasma and kidneys were collected.

Results

 The systolic and diastolic blood pressure, heart rate and glomerular filtration rate remained unchanged. Plasma corticosterone increased in SVEE rats when compared to CON group. Plasma 8-isoprostane, a systemic marker of oxidative stress, increased while total antioxidant capacity decreased in SVEE but not in CON. Kidney cortical tissue homogenates exhibited increase in superoxide, hydrogen peroxide and protein carbonylation in SVEE but not CON, all indicative of heightened oxidative stress. Renal cortical mitochondrial SOD activity was significantly reduced in SVEE than CON.

Conclusion

 Significant decline in mitochondrial respiration and oxygen consumption was observed, in addition to low ATP, reduced ATP synthase and cytochrome C oxidase levels, as well as accelerated mitochondrial fission, and reduced fusion processes, were observed in SVEE than CON rats, all indicative of renal mitochondrial impairment.

KEYWORDS:

• Vehicle exhaust
• air pollution
• kidney
• mitochondria
• oxidative stress

Acknowledgments

This manuscript is dedicated to the memory of Dr. Mohammad Asghar (10/12/1966-2/2/2019), who made significant contributions to the field of renal physiology and continued to work in this area until his passing from lung cancer. This manuscript is his last one which was due for submission a few days before his passing.

Additional information

Funding

This work was supported by the NIH/NIA under Grant number AG039836; NIH/NIA under Grant number 1R15AG05702401A1; GEAR award, University of Houston.