The Effect of Chronic Cigarette Smoking on the Kidneys in Male Mice and In Ovariectomized and Non-Ovariectomized Female Mice

Abstract

Chronic Cigarette Smoking (CS), a well-known risk factor for numerous diseases, has been shown to play a significant influence in renal disorders in both females and males. The progression of chronic kidney disease (CKD) may change depending on gender. According to national US reports, men died from CKD at a higher rate than women in most states. In accordance, premenopausal women are less prone to CKD due to the presence of estrogen. Estrogen is known to be nephroprotective and exerts its effect on several aspects. The objective of this study is to examine the effects of CS on the kidneys and to assess the involvement of estrogen in that regard. Age-matched C57BL/6J female and male mice were divided into 5 groups: 1) Male control group; 2) Male CS group; 3) Female control group; 4) Female CS group, and 5) Ovariectomized female CS group. Cardiac systolic function was evaluated, and kidneys were subjected to histological and molecular analysis. Hemodynamic cardiac assessment revealed an enhanced heart workload characterized by a marked elevation in blood pressure and cardiac output in ovariectomized female group. Our renal findings indicate that females are more prone to morphological alterations and fibrosis following CS as evidenced by a significant increase in bowman’s capsule area, a remarkable retraction in the glomerular capillary area, and a remarkable decrease in the proximal tubule area in both CS females and CS ovariectomized groups. On the other hand, these parameters weren’t affected following CS in males. Moreover, CS female and CS ovariectomized female groups exhibited a significant increase in renal fibrosis paralleled with a decrease in renal mRNA expression of MMP-2 and MMP-9 levels. These expressions were reversed in CS male group. In addition, there was a significant decrease in α-smooth muscle actin (α-SMA) protein level, a renal pro-fibrotic marker, in males. However, renal inflammatory assessment showed that CS males are more prone to inflammation with a marked decrease in the anti-inflammatory IL-4 protein levels and a substantial rise in the pro-inflammatory TNF-α mRNA expression levels. In Conclusion, following 8 weeks of CS, the female kidneys seem to experience prominent morphological alterations while males seem to have an imbalanced inflammatory profile. Although the ovariectomized CS females were hemodynamically affected two days post-CS cessation, at the level of the kidneys, the estrogen effect seems to be masked in the presence of CS as such results were more likely consistent with the ovariectomized CS female.