Melasma is a common aesthetic problem characterized by facial hyperpigmentation. It frequently affects young to middle-aged females who are Hispanic or of Asian, African or Middle Eastern descent. Its pathogenesis is still mysterious with multiple factors are being accused to play a role. Although many treatment options are currently available, melasma is difficult to cure with tendency to relapse. Melasma (a term derived from the Greek word “melas” meaning black) is a worldwide prevalent acquired disorder of hyperpigmentation that commonly affects females with Fitzpatrick skin phototypes III-V (Goh and Dlova, 1999 and Gupta et al., 2006). It is characterized by appearance of symmetrical light to dark brown spots and patches on sun exposed areas mostly the face and especially the forehead, cheeks and chin (Kang and Ortonne, 2009). Melasma is sometimes termed chloasma (derived from the Greek word “chloas” meaning green) or mask of pregnancy when it develops in pregnant females (Handel et al., 2014a).

Melasma is a common aesthetic problem characterized by facial hyperpigmentation. It frequently affects young to middle-aged females who are Hispanic or of Asian, African or Middle Eastern descent. Its pathogenesis is still mysterious with multiple factors are being accused to play a role. Although many treatment options are currently available, melasma is difficult to cure with tendency to relapse. Melasma (a term derived from the Greek word “melas” meaning black) is a worldwide prevalent acquired disorder of hyperpigmentation that commonly affects females with Fitzpatrick skin phototypes III-V (Goh and Dlova, 1999 and Gupta et al., 2006). It is characterized by appearance of symmetrical light to dark brown spots and patches on sun exposed areas mostly the face and especially the forehead, cheeks and chin (Kang and Ortonne, 2009). Melasma is sometimes termed chloasma (derived from the Greek word “chloas” meaning green) or mask of pregnancy when it develops in pregnant females (Handel et al., 2014a).

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Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted.

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