Kidney Dysfunction, Biochemical Changes, DNA Alteration, and MAPKs Regulation Following Chronic Exposure to Regular and Occasional Hookah Smoke in Mice

Regular hookah smoking (Reg-HS) has become a major global public health issue, linked to significant health risks, including kidney damage. A less frequent pattern of use, known as occasional hookah smoking (Occ-HS), is also common; however, there has been little progress in understanding the direct impact of Occ-HS on kidneys. To investigate how varying frequencies of HS inhalation affect the kidney, we exposed mice to nose-only HS under two regimens, occasional (30 min once weekly) and regular (30 min five times per week) for a duration of 6 months. This study explored the impact on renal damage, inflammatory responses, oxidative stress levels, genotoxicity, and mitochondrial activity as well as the possible modulation of MAPK signaling pathway. Both Occ-HS and Reg-HS led to a marked elevations in plasma levels of urea and creatinine (<i>p</i> < 0.05-<i>p</i> < 0.0001). Additionally, concentrations of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly increased in both groups (<i>p</i> < 0.01-<i>p</i> < 0.0001). Notably, only the Reg-HS regimen induced a substantial rise in plasma levels of indoxyl sulfate, cystatin C, and adiponectin (<i>p</i> < 0.01-<i>p</i> < 0.0001). Similarly, relative to the control group, mice subjected to Reg-HS exposure exhibited significantly elevated levels of proinflammatory cytokines, tumor necrosis factor-<i>α</i>, and interleukin-6 (<i>p</i> < 0.0001). Exposure to either Occ-HS or Reg-HS caused significant increase in interleukin-1<i>β</i> (<i>p</i> < 0.05, <i>p</i> < 0.0001), thiobarbituric acid reactive substances (TBARS; <i>p</i> < 0.05, <i>p</i> < 0.0001) compared with air-exposed mice. Our findings revealed that Occ-HS inhalation triggered only a decrease in superoxide dismutase (SOD) activity (<i>p</i> < 0.001). On the other hand, nitric oxide (NO; <i>p</i> < 0.001), SOD (<i>p</i> < 0.0001), and Glutathione (GSH; <i>p</i> < 0.0001) levels were significantly decreased in Reg-HS group. Furthermore, DNA damage marker, 8-Hydroxy-2^'-deoxyguanosine was significantly augmented in both regimens (<i>p</i> < 0.0001). Exposure to both regimens resulted in significant elevation in mitochondrial complexes I, II and III, and IV (<i>p</i> < 0.0001). Increased expression of activation of mitogen-activated protein kinases (MAPKs) was observed exclusively in the Reg-HS group, as evidenced by increased levels of p-JNK, p-p38, and p-ERK (<i>p</i> < 0.001-<i>p</i> < 0.0001). In conclusion, our study is the first to demonstrate that despite the significant differences in the amount of smoke inhaled, both Occ-HS or Reg-HS inhalation deteriorate kidney function and induce oxidative damage, inflammatory response, DNA injury, and mitochondrial impairment with modulation of the MAPK signaling. These findings highlight the importance of further research into the public health risks associated with occasional hookah smoking.