Protective effect of hemin against cadmium-induced testicular damage in rats
Introduction
Cadmium is a wide spread environmental pollutant, arising primarily from battery, electroplating, pigment, plastic and fertilizer industries. Acute and chronic cadmium toxicity is associated with severe damage in various organs, particularly the testes, in both humans and animals (Lauwerys, 1979). Previous studies demonstrated a significant decrease in testicular weights with reduced androgen secretion as a result of exposure to cadmium indicating that testicular endocrine function had been compromised (Gunnarsson et al., 2003, Yang et al., 2006). Oxidative stress and inflammation are the main factors implicated in cadmium-induced tissue injury (Kayama et al., 1995, Oteiza et al., 1999, Gupta et al., 2004). Several antioxidants and anti-inflammatory agents were found to be effective in minimizing cadmium-induced organ damage, including the testes with restoration of testicular steriodogenesis (Min et al., 2002, Kara et al., 2007, Yadav and Khandelwal, 2008).
Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is important for regulating the adaptive protection of tissues against oxidative stress and inflammation (Hangaishi et al., 2000, Morio et al., 2006). Hemin, the HO-1 inducer, was proved effective in protecting against oxidative and inflammatory tissue injuries in various experimental models (Yoneya et al., 2000, Wen et al., 2007, Chen et al., 2008). Recently, pharmacological induction of HO-1 by hemin protected rat testes against ischemia/reperfusion injury resulted from testicular torsion and detorsion (Yang et al., 2007). However, to the best of our knowledge, the effect of hemin against cadmium-induced testicular damage was not yet studied.
Therefore, the present study was conducted to evaluate the protective effect of hemin in testicular injury induced by acute cadmium exposure in rats. Also, the effect of zinc protoporphyrin-IX (ZnPP), the HO-1 inhibitor, on the testicular protective activity of hemin was investigated. For this purpose, serum testosterone level was measured. The oxidant-antioxidant status of testicular tissue was assessed by measuring malondialdehyde (MDA) and reduced glutathione (GSH) levels, and catalase and superoxide dismutase (SOD) activities. The levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in testicular tissue were determined. Also, caspase-3 activity (as an indicator of cell apoptosis) was assessed in testicular homogenates. In addition, light and electron microscopic examinations of testicular tissue were performed.
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Animals
Male Sprague-Dawely rats, weighing 200 ± 10 g were obtained from the Animal House, College of Medicine, Al-Ahsa, King Faisal University. The animals were housed at 24 ± 1 °C, 45 ± 5% humidity and 12 h light–12 h dark cycle. They were supplied with standard laboratory chow and water ad libitum, and left to acclimatize for 1 week before the experiments. The experimental protocol was approved by the Local Animal Care Committee. The experimental procedures were carried out in accordance with international
Effect of hemin on serum testosterone level
The rats received cadmium chloride in a single i.p. dose (2 mg/kg) showed significantly lower serum testosterone level as compared to the control animals. However, the level of serum testosterone was significantly higher in animals received cadmium and treated with hemin in comparison to hemin non-treated group. The effect of hemin was completely abolished by prior administration of ZnPP (Fig. 1).
Effect of hemin on testicular oxidant-antioxidant status
Cadmium administration resulted in a significant increase in lipid peroxidation associated with
Discussion
Cadmium is an environmental and industrial pollutant that adversely affects male reproductive system in humans and animals. Increased production of reactive oxygen species and inflammatory cytokines seems to be crucial in the pathogenesis of tissue injury in response to cadmium exposure (Kayama et al., 1995, Acharya et al., 2008).
In the present study, hemin treatment was started one day before cadmium administration and continued for 3 consecutive days in order to obtain the benefits of both
Conflict of interest
There are none.
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