Introduction: Neuronal cell death and glial cell activation are the main pathological findings induced by seizures secondary to oxidative stress. Previous studies have explained neuronal cell death on the basis of cell necrosis and apoptosis. Recent studies have attributed the neuronal loss to autophagy. The proved antioxidant and antifibrotic effect of nilotinib favours its use in the management of epileptic seizures. Aim of the study was to analyse the neuroprotective and antiepileptic effect of nilotinib and explain its mechanism of action. Material and methods: Forty adult male rats were divided into four groups: control, pentylenetetrazol (PTZ) group (injected with PTZ 60 mg/kg, s.c.), pregabalin (Pregb)-PTZ group (pretreated with pregabalin daily 30 mg/kg; orally for 1 week) and nilotinib (NIL)-PTZ group (pretreated with nilotinib, 25 mg/kg daily for 1 week) prior to PTZ. Seizure latency was evaluated, the hippocampus tissue level of antioxidant enzymes was assessed. The histopathological changes in the hippocampus were studied using hematoxylin and eosin stain and immunohistochemical stain for brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), beclin-1, nuclear factor kappa-B (NF-κB) and Bcl-2-like protein 4 (BAX). Results: Nilotinib induced an increase in the latency of seizures, enhanced the antioxidant levels of the γ-aminobutyric acid and nuclear factor (erythroid-derived 2)-like 2 activities together with the improvement of the hippocampal histology. A reduction was reported for BDNF, GFAP, beclin-1, NF-κB and BAX expression in nerve cells. Conclusions: Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy.

Menopause is an important physiological event associated with structural and functional changes in the kidneys. An animal model of bilateral ovariectomy was used to study the effects of estrogen depletion, replacement and antiestrogen on renal structure and endocrine function. Sixty female rats were divided into six groups; group I was the control group, the remaining five groups underwent ovariectomy: group II received no treatment. The other groups received estradiol in group III, tamoxifen in group IV, estradiol followed by tamoxifen in group V and tamoxifen followed by estradiol in group VI. Serum creatinine, blood urea nitrogen, and endocrine functions of kidney were measured. Tissue samples were examined both microscopically for beta estrogen receptors and ultrastructurally for cell changes. Groups II, IV & VI showed a significant increase in creatinine, blood urea nitrogen, renal malondialdehyde, renal erythropoietin, plasma renin and plasma prostaglandin E2 and a significant decrease in renal antioxidants and serum vitamin D3. Groups III &V had a significant decrease in creatinine, blood urea nitrogen, renal malondialdehyde and renal erythropoietin with an increase in renal antioxidants, plasma prostaglandin E2 and serum vitamin D3. Histopathological and ultrastructural examinations revealed atrophic tubular changes in group II. The changes were less marked in groups III &V and more extensive in groups IV & VI. Estrogen receptor beta staining showed progressively increased expression in the absence of estrogen. Structural and most endocrine functions of the kidney were significantly affected by estradiol deficiency. Estradiol replacement exhibited a protective effect on renal tissue and endocrine functions.

Effects of ribavirin on the structure of peritubular sheath (PS) of seminiferous tubules and on testicular functions were studied. We found that ribavirin at a dose of 4 mg/kg/day for 4 weeks produced a significant reduction in testosterone level (6.3 ± 0.2; P < 0.001) and in spermatogenic score count (3.8 ± 0.2; P < 0.001) compared to control values. The thickness of PS (17.8 ± 1.13) and tubular lumen perimeter (1024.7 ± 67) was significantly increased compared to controls (10.7 ± 0.70; P < 0.001 and 808 ± 25; P = 0.004, respectively). The length of germinal epithelium (411.8 ± 39) and tubular external diameters (1661.8 ± 115) was significantly reduced compared to control values (708.4 ± 40; P < 0.001 and 2358.8 ± 169; P < 0.001, respectively). The basement membranes (BMs) were thickened with great deposition of collagen. Myoid cells showed altered structure and extracellular matrix revealed disorganization by excessive collagen I and IV accumulation. Testicular damage was established histologically. Evidence of apoptosis was detected in germ cells. There was a significant increase in integrated density of Casp-3 expression (38,121,743 ± 1,763,420; P < 0.001) in seminiferous tubules compared to control (24,788,409 ± 1,900,140). It is concluded that ribavirin can cause alterations of the testicular function and structure with increased apoptosis in the tissues after 4 weeks of administration. The damaging effect could be persuaded by destruction of the peritubular sheath.