Abstract

There is a worldwide increase in the popularity of water pipe (shisha) tobacco smoking including in Europe and North America. However, little is known about the effects of water pipe smoke (WPS) exposure on male reproductivity. We have recently demonstrated that WPS exposure in mice induces testicular toxicity including inflammation and oxidative stress. Nootkatone, a sesquiterpenoid found in grapefruit, has antioxidant and anti-inflammatory effects. However, the possible protective effect of nootkatone on WPS-induced testicular toxicity has not been reported before. Here, we tested the effects of treatment of mice with nootkatone on WPS-induced testicular toxicity. Mice were exposed to normal air or WPS (30 minutes/day, for 30 days). Nootkatone (90 mg/kg) was given orally to mice by gavage, 1 h before WPS or air exposure. Nootkatone treatment significantly ameliorated the WPS-induced increase in plasma levels of inhibin, uric acid, and lactate dehydrogenase activity. Nootkatone also significantly mitigated the decrease in testosterone, androgen-binding protein, and estradiol concentrations in the plasma induced by WPS. In testicular homogenates, WPS exposure caused a decrease in the total nitric oxide level and an increase in the proinflammatory cytokine interleukin-1β level and oxidative stress markers including malondialdehyde, cytochrome C, and 8-Oxo-2′-deoxyguanosine. All the latter effects were significantly alleviated by nootkatone treatment. Moreover, in testicular homogenate, nootkatone inhibited the expression of nuclear factor-kappaB induced by WPS. Likewise, histological examination of mouse testes showed that nootkatone treatment ameliorated the deterioration of spermatogenesis induced by WPS exposure. We conclude that nootkatone ameliorated the WPS-induced testicular inflammation and oxidative stress and hormonal and spermatogenesis alterations.

Highlights

  • Tobacco consumption is an established major public health problem that results in substantial morbidity and mortality [1, 2]

  • water pipe smoke (WPS) exposure, slightly increased the relative testis weight, an effect that was significantly mitigated by nootkatone concomitant treatment

  • As far as we are aware, there are no data on the effect of WPS on human reproduction

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Summary

Introduction

Tobacco consumption is an established major public health problem that results in substantial morbidity and mortality [1, 2]. Water pipe smoking (WPS) ( termed huqqa, sheesha, nargilah, hubble-bubble, and qalyan), an ancient and common method of tobacco consumption in Asia and North Africa [3, 4], is regaining widespread global popularity, especially among the young population in Western countries [5, 6]. It involves passage of air that is heated by charcoal across tobacco flavored by or sweetened with either fruit or molasses sugar, which makes the smoke more aromatic than cigarette smoke. The smoke produced from the heated tobacco in WPS is or even more toxic than cigarette smoke [7, 8]. Nootkatone (C15H22O) is a sesquiterpenoid isolated from some plants such as grapefruit and rhizomes of Cyperus rotundus and has been reported before to significantly

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