Combined protective effect of zinc oxide nanoparticles and melatonin on cyclophosphamide-induced toxicity in testicular histology and sperm parameters in adult Wistar rats

Background: Cyclophosphamide [CP] has been known as an anticancer drug with several side effects on various organs such as a male reproductive system that can cause infertility

Objective: To evaluate the possible combined effects of zinc oxide nanoparticles [nZno] and melatonin [Mel] on sperm parameters and histopathological changes of the testis in CP-treated rats

Materials and Methods: 42 adult male Wistar rats were divided into six groups. GI: control, GII: 60 mg/kg/wk CP, GIII and GIV, 10 mg/kg/wk Mel and 5mg/kg/wk nZno and GV: 5 mg/kg/wk nZno and 10 mg/kg/wk Mel were given 2 hr prior to CP injection, respectively, GVI: 5mg/kg/wk nZno and 10 mg/kg/wk Mel simultaneously. After 8 wk of treatment, rats were sacrificed and testis and epididymis were harvested for further evaluation

Results: The CP-treated group showed significant decreases in the body, testes and epididymis weights and sperm parameters [sperm count, viability, motility] with an increase abnormal sperms when compared with the control [p<0.001], as well as many histological alterations included decreased diameters of seminiferous tubules and Johnsen's Testicular Score [with degeneration, desquamation, multi-nucleated giant cell formation], whereas combined treatment [GV], showed more protective effects on CP-induced reproductive system damage compared with groups III or IV [p<0.001]

Conclusion: These results suggest simultaneous administration of Mel and nZno have more effectively protections against CP-induced reproductive damage than Mel or nZno alone

Endothelial vasodilator angiotensin receptors are changing in mice with ageing

The vascular function of Angiotensin II-type-2 receptors in adults is controversial. We sought their location and function in mouse aortic rings at young and old mice. Male C57Bl mice [aged 4 and 14 months] were killed by CO2. The descending thoracic aorta was cleaned and dissected into rings. Aortic rings were mounted in Krebs' solution at 37[degree sign]C and then setup in a multi-myograph. Also segments of aorta were incubated with or without antagonists then TMRAngiotensin II and/or QAPB were added. At 4 months, angiotensin II, at low concentrations, caused losartansensitive contraction; higher concentrations [100nmol/L] caused relaxation sensitive to endothelial denudation, L-NAME or PD123319. Angiotensin II-type-1 receptors blockade plus L-NAME revealed PD123319-sensitive contraction. At old mice, aortic relaxation to angiotensin II was lost. At young mice, Losartan and PD123319, together but not separately, abolished binding of fluorescent TMRangiotensin II, to endothelium and smooth muscle, indicatin Angiotensin II-type-1 and Angiotensin II-type-2 receptors in both cell types. In contrast, at 14 months endothelial fluorescence was eliminated by losartan. Aortic endothelium of young adult mice has Angiotensin II-type-2 receptors that release vasodilator nitric oxide. This is lost in old age, explaining age-related loss of vasodilatation by Angiotensin II. Aortic smooth muscle has pro-contractile Angiotensin II-type-1 and Angiotensin II-type-2 receptors in young and old mice. Reciprocal actions of angiotensin II are, due to Angiotensin II-type- 1 and Angiotensin II-type-2 receptors situated on different cell types but only at young ages, Angiotensin II-type-1 receptors of unknown function are present on endothelium

Prevention of di [2-ethylhexyl] phthalate-induced testicular disturbance in mice by Co-administration of L-carnitine

di [2-ethylhexyl] phthalate [DEHP] is widely used in the plastic industry and can induce reproductive toxicity. On the other hand, L-carnitine [LC] plays a crucial role in sperm metabolism and maturation. This study evaluates the effect of LC on body and testis weight, testis tissue, count, motility, viability, morphology, and chromatin quality of epididymal sperm, testicular spermatid number [TSN] per gram testis and daily sperm production [DSP] in LC-treated mice. In this experimental study, adult male NMRI mice [mean age: 4 weeks] were given doses of DEHP and LC by gavaging for 2 weeks. All samples were assessed according to World Health Organization [WHO] criteria. Sperm morphology was assessed using Papanicolaou staining and sperm chromatin quality by aniline-blue staining. The left testes were fixed in Bouin? solution for histological examination and the end slices were stained with hematoxylin and eosin [H and E]. The right testes were homogenized, and then TSN and DSP were calculated with an improved Neubauer haemocytometer and respective frames. Paired t-test, ANOVA, and Kruskal-Wallis tests were utilized for data analysis. Co-administration of DEHP and LC not only prevented significant gains in testicular weight, but also maintained the sperm's normal morphology and chromatin quality [p<0.05]. In addition, LC recovered histological changes, TSN, DSP, and sperm count. These results demonstrated that oral administration of LC partially or generally protects spermatogenesis from DEHP-toxicity in mice