Nose-Only Water-Pipe Smoke Exposure in Mice Elicits Renal Histopathological Alterations, Inflammation, Oxidative Stress, DNA Damage, and Apoptosis.

Abderrahim Nemmar,Ernest Adeghate,Javed Yasin,Badreldin H Ali,Priya Yuvaraju,Sumaya Beegam

doi:10.3389/fphys.2020.00046

Abderrahim Nemmar, Ernest Adeghate + Show 4 more

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https://doi.org/10.3389/fphys.2020.00046

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Abstract

The prevalence of water-pipe tobacco smoking is increasing worldwide, and is relatively high among youth and young adults. Exposure to water-pipe smoke (WPS) has been reported to affect various systems including the respiratory, cardiovascular and reproductive systems. However, the impact of WPS exposure on the kidney has received only scant attention. Here, we assessed the effect of nose-only WPS exposure for one or four consecutive weeks on renal histology, inflammation, oxidative stress, DNA damage, and apoptosis. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Light and electron microcopy analysis revealed that the WPS exposure (especially at 4-week time point) caused degeneration of the endothelial cells of the glomerular capillaries and vacuolar degenerations of the proximal convoluted tubules. WPS exposure also significantly decreased the creatinine clearance, and significantly increased proteinuria and urinary kidney injury molecule-1 (KIM-1) concentration. Kidney lipid peroxidation, reactive oxygen species, and oxidized glutathione were significantly increased. WPS exposure also affected the concentration of reduced glutathione and the activity of catalase. Likewise, renal concentrations of interleukin (IL)-6, IL-1β and KIM-1 were augmented by WPS exposure. Moreover, WPS caused DNA damage as evaluated by comet assay, and increased the expression of cleaved caspase-3 and cytochrome C in the kidney. We conclude that exposure of mice to WPS caused renal histopathological alterations, inflammation, oxidative stress, DNA damage, and apoptosis. If the latter findings could be substantiated by controlled human studies, it would be an additional cause for disquiet about an established public health concern.

Highlights

The consumption of tobacco is considered to be a major public health problem causing substantial morbidity and mortality
We have recently demonstrated that exposure to water-pipe smoke (WPS) in mice causes impairment of lung function, thrombotic events, and triggers inflammation and oxidative stress in various organs including the lung, heart, and testes (Nemmar et al, 2013c,d, 2016a, 2017a; Ali et al, 2017)
We showed that exposure to WPS in mice caused biochemical, histopathological and molecular kidney changes, including degeneration of the endothelial cells of the glomerular capillaries and vacuolar degeneration of the proximal convoluted tubules, oxidative stress, inflammation, DNA damage, and apoptosis

Summary

Introduction

The consumption of tobacco is considered to be a major public health problem causing substantial morbidity and mortality. It is well known that CS affects multiple organ systems resulting in pulmonary and extrapulmonary adverse effects (GBD 2015 Tobacco Collaborators, 2017). In this context, it is wellestablished that CS is responsible for most of lung cancer cases and is the major risk factor for the development of chronic obstructive pulmonary disease, pulmonary edema, recurrent infections, and cardiovascular diseases (GBD 2015 Tobacco Collaborators, 2017). Data from a meta-analysis of prospective cohort studies showed that CS was linked with an increased risk of kidney disease in the general population (Xia et al, 2017) The latter findings were independent of well-known risk factors for kidney disease such as age, hypertension, diabetes mellitus, and body mass index (Xia et al, 2017)

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