Effects of zinc deficiency on impaired spermatogenesis and male infertility: the role of oxidative stress, inflammation and apoptosis.

Zinc (Zn) is necessary for the normal function of the male reproductive system and spermatozoa. Although influences of zinc deficiency on impaired spermatogenesis and male infertility have been widely considered, the molecular and cellular mechanisms of these abnormalities are not well understood. General abnormalities, including hypogonadism, Leydig cells damage, deficiency of sex hormone production and impaired spermatogenesis, as well as inflammation, antioxidant depletion, sperm death and male infertility can be observed during zinc deficiency. However, it is not obvious which pathways are relevant to the pathogenesis of zinc deficiency. Oxidative stress (OS) induced by reactive oxygen species is likely as the main mechanism of zinc deficiency which is associated with sperm DNA fragmentation, decrease in sperm membrane integrity, apoptosis, depletion of antioxidants, and consequently poor sperm quality and male infertility. Therefore, identification of these pathways will give valuable information regarding the mechanisms of zinc deficiency on the male reproductive system and the potential way for developing a better clinical approach. In this review, we aim to discuss the proposed cellular and molecular mechanisms of zinc deficiency on the male reproductive system, the importance of OS and mechanisms by which zinc deficiency induces OS and depletion of other antioxidants.

Role of oxidative stress and antioxidant therapy in acute and chronic phases of sulfur mustard injuries: a review.

Sulfur mustard (SM) is a chemical compound that preferentially targets ocular, cutaneous and pulmonary tissues. Although pathologic effect of SM has been extensively considered, molecular and cellular mechanism of its toxicity, especially at the chronic phase of injury is not well-understood. Excessive production of reactive oxygen species (ROS) and oxidative stress (OS) appears to be involved in SM-induced injuries. SM may trigger several molecular and cellular pathways linked to OS and inflammation that can subsequently result in cell death and apoptosis. At the acute phase of injury, SM can enhance ROS production and OS by reducing the activity of antioxidants, depletion of intercellular glutathione (GSH), decreasing the productivity of GSH-dependent antioxidants, mitochondrial deficiency, accumulation of leukocytes and pro-inflammatory cytokines. Overexpression of ROS producing enzymes and down-regulation of antioxidant enzymes are probably the major events by which SM leads to OS at the chronic phase of injury. Therefore, antioxidant therapy with potent antioxidants such as N-acetylcysteine and curcumin may be helpful to mitigate SM-induced OS damages. This review aims to discuss the proposed cellular and molecular mechanisms of acute and delayed SM toxicity, the importance of OS and mechanisms by which SM increases OS either at the acute or chronic phases of injuries along with research on antioxidant therapy as a suitable antidote.

Niosomal carriers enhance oral bioavailability of carvedilol: effects of bile salt-enriched vesicles and carrier surface charge.

Carvedilol (CRV) is an antihypertensive drug with both alpha and beta receptor blocking activity used to preclude angina and cardiac arrhythmias. To overcome the low, variable oral bioavailability of CRV, niosomal formulations were prepared and characterized: plain niosomes (without bile salts), bile salt-enriched niosomes (bilosomes containing various percentages of sodium cholate or sodium taurocholate), and charged niosomes (negative, containing dicetyl phosphate and positive, containing hexadecyl trimethyl ammonium bromide). All formulations were characterized in terms of encapsulation efficiency, size, zeta potential, release profile, stability, and morphology. Various formulations were administered orally to ten groups of Wistar rats (n=6 per group). The plasma levels of CRV were measured by a validated high-performance liquid chromatography (HPLC) method and pharmacokinetic properties of different formulations were characterized. Contribution of lymphatic transport to the oral bioavailability of niosomes was also investigated using a chylomicron flow-blocking approach. Of the bile salt-enriched vesicles examined, bilosomes containing 20% sodium cholate (F2) and 30% sodium taurocholate (F5) appeared to give the greatest enhancement of intestinal absorption. The relative bioavailability of F2 and F5 formulations to the suspension was estimated to be 1.84 and 1.64, respectively. With regard to charged niosomes, the peak plasma concentrations (Cmax) of CRV for positively (F7) and negatively charged formulations (F10) were approximately 2.3- and 1.7-fold higher than after a suspension. Bioavailability studies also revealed a significant increase in extent of drug absorption from charged vesicles. Tissue histology revealed no signs of inflammation or damage. The study proved that the type and concentration of bile salts as well as carrier surface charge had great influences on oral bioavailability of niosomes. Blocking the lymphatic absorption pathway significantly reduced oral bioavailability of CRV niosomes. Overall twofold enhancement in bioavailability in comparison with drug suspension confers the potential of niosomes as suitable carriers for improved oral delivery of CRV.