Fenofibrate ameliorates testicular damage in rats with streptozotocin-induced type 1 diabetes: role of HO-1 and p38 MAPK.

BACKGROUND: Since diabetes mellitus type-1 (DM-1) induces testicular oxidative and inflammatory damage with finally an ultimate male infertility, and as fenofibrate (FEN) plays an important antioxidant and anti-inflammatory role, the aim of the present study was to investigate the effects of FEN on diabetes-induced reproductive damage and clarifying the underlying related mechanisms. METHODS: DM-1 was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50 mg/kg). FEN (100 mg/kg/day, orally) was administrated to diabetic rats for 4 weeks. Testicular damage was detected by estimation of both testicular and body weights, assessment of serum testosterone, testicular oxidative stress parameters (malondialdehyde and nitric oxide levels) and testicular oxidant defenses (reduced glutathione, superoxide dismutase and hemeoxygenase-1). Expressions of the inflammatory markers (inducible nitric oxide synthase, p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor alpha, interleukin-6 and apoptotic marker (caspase-3) were evaluated in testicular tissue. Our results were confirmed by histopathological examination of testicular tissues. RESULTS: Diabetic testicular damage was proved by both biochemical and histopathological examinations. FEN treatment reversed diabetic testicular damage; normalized the serum testosterone level, improved anti-oxidative capacity, ameliorated the pro-inflammatory cytokine expression in testicular tissue with the down regulation of p38 MAPK mediated-testicular apoptosis. CONCLUSION: FEN treatment exerted a protective effect against streptozotocin-induced diabetic reproductive dysfunction not only through its powerful antioxidant and hypoglycemic effects, but also through its anti-inflammatory and anti-apoptotic effect via down-regulation of testicular p38 MAPK expression in diabetic rats.

The possible structural changes in the adrenal gland cortex after induction of hepatic ischemia-reperfusion injury in male albino rats: Light and electron microscopic study.

The adrenal gland is an important endocrine gland in the body that secrets the adrenal hormones. One of the important clinical issues is the hepatic ischemia-reperfusion (IR) injury. Liver IR injury results in many distant organs dysfunctions such as lung, kidney, intestine, pancreas, and myocardium. The aim of the present study was to investigate the possible remote effects of hepatic IR on the structure of the adrenal cortex. Twenty healthy males, Sprague-Dawley albino rats aged 6-8 weeks were randomly divided into two groups (10 rats each): the sham control group (SC-group) and the ischemia-reperfusion group (IR-group). Sera were estimated for the following: aspartate transaminase (AST), alanine transaminase (ALT), lactic dehydrogenase (LDH), and corticosterone levels. Also oxidative markers such as malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), and the antioxidative enzyme, catalase were measured. Adrenal glands were processed for light and transmission electron microscopic study. The results showed a significant increase in serum liver enzymes (AST, ALT, and LDH), corticosterone, MDA, and TNF-α levels and a significant decrease in serum levels of catalase in IR-group compared with SC-group. Adrenal cortical tissue of IR-group showed the loss of normal appearance. Some cells of zona glomerulosa and most of the zona fasciculata cells appeared swollen and degenerated with highly vacuolated cytoplasm. Other cells were shrunken with deeply acidophilic cytoplasm and pyknotic nuclei. Degenerated mitochondria with disrupted cristae, lipid droplets were confluent and dilated smooth endoplasmic reticulum were seen. Few zona reticularis cells had the dark nucleus and cytoplasmic vacuolations. In the different zones, blood capillaries were markedly congested and some inflammatory cells infiltrations were observed. Liver IR affected the structure of the adrenal cortex.

Possible protective effect of curcumin on the thyroid gland changes induced by sodium fluoride in albino rats: light and electron microscopic study.

OBJECTIVES: Thyroid gland regulates the body's metabolic rate and plays an exquisitely important role in the human health. Fluoride exposure can affect thyroid function. Curcumin is a potent antioxidant that works through several mechanisms. The aim of the present study was to demonstrate the hormonal, histological, and ultrastructural changes occurred in the thyroid gland induced by exposure to sodium fluoride (NaF) and study the possible protective effect of curcumin on the NaF-induced effects. METHODS: Thirty male albino rats were randomly divided into 3 equal groups (10 rats each): the control group, NaF group, and NaF+Curcumin (NaF+Cur) group. Thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) levels were assayed and thyroid tissues processed for light and transmission electron microscopic study. RESULTS: In NaF group, serum T3 and T4 levels were significantly decreased whereas TSH level was significantly increased compared to the control group. Thyroid tissues showed flattening of the epithelial lining with several follicular cell degenerations, hyperplasia, decreased colloid, disrupted basement membrane, cytoplasmic vacuolations, degenerated mitochondria, widening of rough endoplasmic reticulum cisternae, and vascular congestion compared to the control group. In the NaF+Cur group, serum TSH levels were significantly decreased in comparison with NaF group and no significant difference in comparison with the control group. Thyroid sections appeared apparently normal compared to the control group and NaF group. CONCLUSIONS: Sodium fluoride affected both the function and structure of the thyroid gland while curcumin was protective against these toxic effects.