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Numerous reports demonstrate that cadmium (Cd) induces oxidative stress by increasing lipid peroxidation and altering antioxidative enzymes status. Thirty male rats were subdivided into control-saline, Cd-saline and Cd-ghrelin groups. A single dose of Cd was injected to induce testicular injury and also ghrelin for 10 consecutive days to group 3. SOD activity decreased and lipid peroxidation increased by Cd administration. The mean activities of GPx and CAT as well as GSH content were lower in the Cd-saline rats; however, they did not statistically differ compared with the controls. Exposure to Cd resulted in complete degeneration of seminiferous tubules with severe depletion of germ cells and arrest in spermatogenesis. Notably, ghrelin treatment not only prevented reduction in SOD, GPx, CAT and GSH level, but also increased enzyme activities form their normal values. Moreover, TBARS concentration was significantly reduced by ghrelin administration. Furthermore, ghrelin pre-treatment resulted in partial but not significant prevention in testicular histopathological features damaged by Cd. In conclusion, the obtained results indicate for the first time the novel evidences of ghrelin ability in promotion of antioxidant enzyme activities and reduction of lipid peroxidation following Cd-induced oxidative stress in the rat testis. These observations also demonstrate that ghrelin may be considered as promising antioxidant agent in prevention and attenuation of testicular injury upon Cd toxicity., (© 2014 Blackwell Verlag GmbH.)

Background: Cryptorchidism is associated with increased level of reactive oxygen species and lipid peroxidation. This study was undertaken to examine the possible ghrelin ability in attenuation of testicular damage in response to elevated temperature., Methods: Thirty male rats were subdivided into sham-operated, cryptorchidism-saline and cryptorchidism-ghrelin group. Bilateral cryptorchidism was induced in groups 2 and 3, surgically. The animals in group 3 were given ghrelin for 7 days and all testes were taken for biochemical and photomicrograph analysis., Results: Glutathione peroxidase activity and glutathione content significantly promoted on day 7 in the cryptorchid rats treated by ghrelin. Catalase activity was higher in the ghrelin-exposed animals than the cryptorchidism-saline group on both experimental days. Although superoxide dismutase activity was elevated by ghrelin treatment on both days, it did not differ significantly. By contrast, significant reduction was observed in thiobarbituric acid reactive substances concentrations following ghrelin administration on day 7. Moreover, ghrelin could improve histopathological scores of the testes, and diminished formation of giant cells and tubular vacuolization., Conclusions: These findings indicate for the first time the novel evidence of ghrelin antioxidant properties in attenuation of rat testicular injury following experimentally induced cryptorchidism., (© 2014.)

More recently, we have reported the beneficial effects of ghrelin in improvement of histopathological features of the rat testis following local heat exposure. However, the exact mechanism and the precise role of apoptosis- and proliferation-specific proteins in this regeneration process remained to be explored. Thus, thirty adult male Wistar rats were allotted for the experiment and subdivided equally into three groups: control-saline (CS), heat-saline (HS) and heat-ghrelin (HG). The scrota of HS and HG groups were immersed once in water bath at 43°C for 15 min. HG animals received 2 nmol of ghrelin subcutaneously immediately after heating every other day until day 60 and the other groups were given physiological saline using the same method. The testes of all groups were taken after rat killing on days 30 and 60 after heat treatment for immunocytochemical detection of pro-apoptotic factor Bax, anti-apoptotic protein Bcl-2 and proliferation-associated peptide PCNA in the germ cells. Ghrelin could significantly suppress the Bax expression in spermatocytes compared to the HS group at day 30 (P<0.05). Likewise, the mean percentages of spermatogonia containing Bax substance were lower in ghrelin-exposed animals, however the differences were not statistically significant. There were immunoreactive cells against Bcl-2 in each germ cell neither in the control nor in the heated animals of experimental groups. In contrast, the number of PCNA immunolabeling cells were higher in HG group in compared to HS or CS animals on both experimental days (P<0.001). Down-regulation of Bax expression concurrent with overexpression of PCNA in HG group indicates the ability of ghrelin in acceleration of testicular germ cells regeneration following heat stress. These findings indicate that ghrelin may be used as a novel and efficient antioxidant agent to induce resumption of spermatogenesis upon environmental heat exposure., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n=7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P<0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact, ghrelin balanced Bax/Bcl-2 ratio toward at increase of Bax level in the spermatocytes and therefore may stimulate apoptosis in these germ cells. In contrast, ghrelin administration significantly suppressed proliferation-associated peptide PCNA in the spermatocytes as well as spermatogonia (P<0.05). Whereas, caspase-3 activity did not show any marked alteration during the experiment in both groups (P>0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Antioxidant properties of ghrelin have been recently reported on various oxidative stresses in limited tissues. This study was set to examine the possible antioxidative effects of ghrelin in rat ovarian tissue. Twenty eight female adult Wistar rats were randomly allocated into control and treatment groups. Treatment group (n=14) received 2nmol of ghrelin as subcutaneous injection for 14 consecutive days or vehicle (physiological saline) to the control rats. The animals from both groups were equally killed on days 9 and 14 after beginning of ghrelin injection (n=7 from each group on each day) and their ovaries were taken for later antioxidant enzyme activity assays as well as measurement of glutathione content and thiobarbituric acid reactive substances (TBARS) level. Superoxide dismutase activity was significantly higher on days 9 (P<0.05) and 14 (P<0.01) in the treated group compared to the control rats. By contrast, lipid peroxidation, as TBARS value, reduced significantly on both experimental days in the ghrelin-exposed animals (P<0.05). Although, the mean activity of catalase and glutathione content was greater in the treated rats, however, the differences were not statistically significant. Slight changes occurred in glutathione peroxidase activity during the experimental period and there were no differences either on day 9 or on day 14 between groups. In conclusion, the results of the present investigation indicate for the first time the novel evidence of antioxidant properties of ghrelin in the rat ovary., (Copyright 2010 Elsevier B.V. All rights reserved.)

Ghrelin has recently been reported to exert beneficial effects on various oxidative stresses as a result of its antioxidant properties. Therefore, we designed this study to explore the probable antioxidative effects of this peptide in the testis. Twenty-eight male adult Wistar rats were divided into equal control and treatment groups. In the treatment group, 1 nmol of ghrelin was administered as subcutaneous injection for 10 consecutive days or vehicle (physiological saline) to the control rats. The control and treated rats were killed on days 6 and 10 after beginning of ghrelin injection (n = 7 from each group on each day). The testes were taken and measured for antioxidant enzyme activity and malondialdehyde (MDA) content. Glutathione peroxidase activity significantly increased on day 10 in the treated animals compared with the control group (P < 0.05). Although the mean activity of glutathione peroxidase was greater on day 6 in the ghrelin-treated group than in the control animals, it was not statistically significant. There were no significant differences in superoxide dismutase and catalase activities between the groups. However, MDA level decreased by ghrelin treatment on day 10 compared with the control rats (P < 0.05). The results of this study indicate for the first time novel evidences for antioxidant properties of ghrelin in the rat testis.