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Zoledronic acid (ZLD) is a bisphosphonate drug widely administered against pathological conditions such as hypercalcemia of malignancy, osteoporosis, bone metastases from solid tumors, and multiple myeloma. Unfortunately, renal injury is a serious and dose-limiting adverse effect of ZLD. There is no specific mechanism for ZLD-induced renal damage. The current study aimed to assess the effects of ZLD (10 and 15 mg/kg, i.p., single dose) on the rat kidney. In this regard, several parameters, including oxidative stress biomarkers, serum level of BUN and creatinine, inflammatory cytokines, kidney histopathology, and indices of mitochondrial function were assessed. A significant increase in serum Cr and BUN revealed renal injury. Moreover, kidney histopathological changes, including interstitial inflammation, tissue necrosis, and tubular atrophy, were detected in ZLD-treated rats. Biomarkers of oxidative stress, including a significant increase in reactive oxygen species (ROS), depletion of kidney glutathione (GSH) stores, increased lipid peroxidation, and suppression of the total antioxidant capacity, were detected in ZLD-treated animals. ZLD also significantly increased renal levels of TNF-α, IL-6, and IL-1β. ZLD exposure was also associated with significantly decreased mitochondrial dehydrogenases activity, mitochondrial depolarization, mitochondrial permeabilization, and ATP depletion. These data highlight mitochondrial dysfunction, inflammatory response, and oxidative stress as potential mechanisms in ZLD-induced kidney injury.

Melasma is a chronic hyperpigmentation skin disorder that is more common in the female gender. Although melasma is a multifactorial skin disorder, however, sun-exposure and genetic predisposition are considered as the main etiologic factors in melasma occurrence. Although numerous topical and systemic therapeutic agents and also non-pharmacologic procedural treatments have been considered in melasma management, however, the commonly available therapeutic options have several limitations including the lack of sufficient clinical effectiveness, risk of relapse, and high rate of unwanted adverse drug reactions. Recruitment of nanotechnology for topical drug delivery in melasma management can lead to enhanced skin penetration, targeted drug delivery to the site of action, longer deposition at the targeted area, and limit systemic absorption and therefore systemic availability and adverse drug reactions. In the current review, first of all, the etiology, pathophysiology, and severity classification of melasma have been considered. Then, various pharmacologic and procedural therapeutic options in melasma treatment have been discussed. Afterward, the usage of various types of nanoparticles for the purpose of topical drug delivery for melasma management was considered. In the end, numerous clinical studies and controlled clinical trials on the assessment of the effectiveness of these novel topical formulations in melasma management are summarized.