Biochemical and histological study on the effect of levetiracetam on the liver and kidney of pregnant albino rats.

BACKGROUND: Levetiracetam is a broad-spectrum antiseizure agent and one of the most commonly prescribed drugs for epilepsy. The aim of this work was to assess the effect of levetiracetam at its therapeutic range on the liver and kidney of pregnant albino rats. MATERIALS AND METHODS: Forty pregnant rats were divided equally into two groups (I-II), Rats in the group I were gavaged 1.5 mL/day distilled water in two divided doses throughout pregnancy. Rats in the group II were gavaged 1.5 mL/day distilled water (containing 36 mg levetiracetam) in two divided doses throughout pregnancy. At the end of the experiment, blood samples were taken and the sera were separated and used for biochemical analysis. The kidneys and livers of both groups were excised and used for light and electron microscopic examination. RESULTS: Treatment with levetiracetam induced undesirable histopathological changes in the liver and kidney of pregnant albino rats. These changes were in the form of distortion of the hepatic architecture, dilatation of the central and the portal veins, widening of the Bowman's spaces, thickening and disruption of the glomerular basement membrane, fusion and effacement of secondary foot processes, cytoplasmic vacuolation, and swollen mitochondria with loss of their cristae. Such changes were confirmed by alteration of certain biochemical parameters related to the liver and kidney functions. CONCLUSIONS: Levetiracetam induced deleterious effects on the liver and kidney of pregnant albino rats. Further investigations are recommended to clarify the mechanism of levetiracetam toxicity.

Endothelial dysfunction marker YKL-40 is elevated in male patients with idiopathic infertility.

Metabolic syndrome represents a collection of cardiovascular risk factors, including overweight, hypertension, dyslipidemia and impaired glucose metabolism, with insulin resistance. In recent years, the potential relationship between metabolic syndrome and male factor infertility has been studied. As endothelial dysfunction is the hallmark of metabolic syndrome, the aim of this work was to assess serum levels of YKL-40 as a marker of endothelial dysfunction in male patients with idiopathic infertility. The study revealed that YKL-40 levels were elevated in patients than controls denoting that endothelial dysfunction might play a role in the pathogenesis of idiopathic infertility and that YKL-40 as a marker of endothelial dysfunction could be a useful marker of idiopathic infertility.

Serum relaxin-3 hormone relationship to male delayed puberty.

Puberty is the transitional period between childhood and adulthood, a process encompassing morphological, physiological and behavioural development to attain full reproductive capability. This study aimed to assess serum relaxin-3 hormone relationship with male delayed puberty. Sixty males were investigated as two equal groups: males with delayed puberty and healthy matched males as controls. They were subjected to history taking, clinical examination and estimation of serum FSH, LH, testosterone, relaxin-3 hormonal levels. The results showed that the secondary sexual characters in the patients group were at Tanner stages 1-2 and in the healthy controls at Tanner stages 3-5. The mean BMI in the patients group was significantly increased, whereas the mean levels of the span, testicular volume, serum LH, FSH, testosterone as well as relaxin-3 hormonal levels were significantly decreased compared with the healthy controls. Serum relaxin-3 levels showed significant positive correlation with the age, testis volume, span, Tanner stages, serum testosterone, FSH, LH hormones. In addition, serum relaxin-3 levels showed significant negative correlation with BMI. It is concluded that serum level of relaxin-3 hormone is an important mediator in the pathophysiological process of normal puberty being significantly decreased in males with delayed puberty.

Effects of angiotensin II blockade on inflammation-induced alterations of pharmacokinetics and pharmacodynamics of calcium channel blockers.

BACKGROUND AND PURPOSE: Inflammation elevates plasma verapamil concentrations but diminishes pharmacological response. Angiotensin II is a pro-inflammatory mediator. We examined the effect of angiotensin II receptor blockade on the pharmacokinetics and pharmacodynamics of verapamil, as well as the binding properties and amounts of its target protein in calcium channels, in a rat model of inflammation. EXPERIMENTAL APPROACH: We used 4 groups of male Sprague-Dawley rats (220-280 g): inflamed-placebo, inflamed-treated, control-placebo and control-treated. Inflammation as pre-adjuvant arthritis was induced by injecting Mycobacterium butyricum on day 0. From day 6 to 12, 30 mg kg(-1) oral valsartan or placebo was administered twice daily. On day 12, a single oral dose of 25 mg kg(-1) verapamil was administered and prolongation of the PR interval measured and plasma samples collected for verapamil and nor-verapamil analysis. The amounts of the target protein Ca(v)1.2 subunit of L-type calcium channels in heart was measured by Western blotting and ligand binding with (3)H-nitrendipine. KEY RESULTS: Inflammation reduced effects of verapamil, although plasma drug concentrations were increased. This was associated with a reduction in ligand binding capacity and amount of the calcium channel target protein in heart extracts. Valsartan significantly reversed the down-regulating effect of inflammation on verapamil's effects on the PR interval, and the lower level of protein binding and the decreased target protein. CONCLUSIONS AND IMPLICATIONS: Reduced responses to calcium channel blockers in inflammatory conditions appeared to be due to a reduced amount of target protein that was reversed by the angiotensin II antagonist, valsartan.

Serum leptin correlates in infertile oligozoospermic males.

Leptin is an adipocyte-secreted protein that participates in the regulation of energy homeostasis. Eighty men were investigated; fertile normozoospermia as a control (n = 30) and infertile oligozoospermia (n = 50). The patients underwent estimation of body weight (kg), height (cm), calculation of body mass index (BMI), semen analysis, serum leptin and testosterone hormones. Mean body weight was significantly higher in infertile oligozoospermia compared with controls. Mean height, BMI and serum testosterone levels showed nonsignificant differences between the two groups. Infertile oligozoospermia had significantly higher mean serum leptin level than controls (mean +/- SD; 6.88 +/- 8.65, 16.3 +/- 13.98 ng ml(-1), P < 0.01). Serum leptin demonstrated significant positive correlation with age, body weight, BMI and significant inverse correlation with serum testosterone. It had nonsignificant correlation with the height and sperm concentration. These results are suggestive of a link between the adipocyte derived hormone, leptin and male reproduction.

Effects of Vitamin E pretreatment on subacute toxicity of mixture of Co, Pb, and Hg nitrate-induced nephrotoxicity in rats.

The aim of the study was to prove that Vitamin E has some beneficial effects on the kidneys of rats by protecting them from the toxicity of certain heavy metals. The protective effect of Vitamin E on Co, Pb, or Hg nitrate and a mixture of them induced nephrotoxicity was tested in a 3-months-old Norway strain (inberd) rat (Raltus norvigus) weighing 100-120g. A study was carried out, which comprised one control group and five experimental groups. In this experiment, nitrate salts of Co, Pb, or Hg were administered subcutaneously (s.c.) either alone (0.5mg/100g body weight) for 4 weeks or as a mixture (0.25mg/100g body weight); Vitamin E internal control (250IU/100g body weight) was administered by oral gavage for 4 weeks, Vitamin E pretreatment for 7 days was followed by concomitant administration of Co, Pb, and Hg, respectively and Vitamin E pretreatment for 7 days, followed by concomitant administration of mixture of three heavy metals for 4 weeks. Blood and kidney tissue samples were taken from the control and all the experimental groups for biochemical and histological study. Nephrotoxicity was characterized by histopathological as well as renal function data. The main pathological changes in the kidney after Co administration were shrunken and degeneration of renal tubule cells, disturbance in their position, size, shape, and staining affinity. Treatment with Hg caused desquamation, necrosis, atrophy, and loss of renal tubule cells and glomeruli. Lead intoxication had a profound effect on the structure and consequently on the function of the rat kidney. Most renal tubule cells were very dense, dehydrated with obscure cytoplasmic details. Most nuclei were shrunken and pyknotic. Also, most glomeruli revealed shrinkage and widening of capsular space. On the other hand, subacute exposure with the mixture of the three heavy metals showed marked destruction and distortion of the renal tubule cells. Marked fibrosis between the damaged tubules was also seen. On the other hand in the recovery groups, i.e., in groups II and III, the previously observed histopathological changes were still present with regression of their intensity. Four-week oral administration with Vitamin E (250IU/100g body weight) revealed no abnormal histological findings as compared with the normal kidney of the control animal, except for some Malpighian corpuscles which demonstrated wide capsular space, and spherical masses were seen within the glomeruli. After pretreatment with Vitamin E for 7 days, followed by treatment with (0.5mg/100g body weight ) Co, Pb, or Hg nitrate alone or with their mixture (0.25mg/100g body weight) for 4 weeks, an improvement in the histological changes were observed compared to those previously seen in groups II and III. The glomeruli showed minimal degenerated changes, the tubular arrangement and cytoplasmic basophilia more or less similar to the normal control. It was also found that the heavy metals were investigated both alone and in combination; the serum creatinine and blood urea level were significantly increased, and this elevation was diminished by Vitamin E pretreatment. According to the present results, it is concluded that combined exposure to a mixture of Vitamin E and examined heavy metals can minimize the histological alteration and diminish the serum creatinine and blood urea level. Also, it was found that the rank order of metal cytotoxicities was Hg > Co > Pb.