Ekaterina Pavlova

Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice, subjected to subacute lead intoxication.

In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys>spleen>liver>brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs.

Losartan suppresses the kainate-induced changes of angiotensin AT(1) receptor expression in a model of comorbid hypertension and epilepsy.

Aims: Experimental and clinical studies have demonstrated that components of renin‐angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT1 receptor) in limbic structures, as well as the effect of the AT1 receptor antagonist losartan in a model of comorbid hypertension and epilepsy. Main methods: The expression of AT1 receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE). The effect of losartan was studied on AT1 receptor expression in epileptic rats that were treated for a period of 4 weeks after status epilepticus. Key findings: The naive and epileptic SHRs were characterized by stronger protein expression of AT1 receptor than normotensive Wistar rats in the CA1, CA3a, CA3b, CA3c field and the hilus of the dentate gyrus of the dorsal hippocampus but fewer cells were immunostained in the piriform cortex. Increased AT1 immunostaining was observed in the basolateral amygdala of epileptic SHRs but not of epileptic Wistar rats. Losartan exerted stronger and structure‐dependent suppression of AT1 receptor expression in SHRs compared to Wistar rats. Significance: Our results confirm the important role of AT1 receptor in epilepsy and suggest that the AT1receptor antagonists could be used as a therapeutic strategy for treatment of comorbid hypertension and epilepsy.

Chronic exposure to cobalt compounds — an in vivo study

An in vivo experimental model for testing the effects of long-term chronic treatment with cobalt(II) compounds — cobalt chloride (CoCl2) and cobalt-EDTA (Co-EDTA) on mice at different stages of development was optimized. Pregnant mice and their progeny were treated with daily doses of 75 or 125 mg kg−1 body weight until postnatal day 90. The compounds were dissolved in regular tap water. Mice were sacrificed on days 18, 25, 30, 45, 60 and 90 after birth, which correspond to different stages of their development. Altered organ weight indices (calculated as a ratio of organ weight to body weight) of spleen, liver and kidneys, were found depending on the type of compound used, dose, duration of treatment, and the age of the animals. The results also showed significant accumulation of cobalt ions in blood plasma, spleen, liver and kidneys of the exposed mice. More Co(II) was measured in the organs of the immature mice (day 18, 25 and 30 pnd) indicating that they were more sensitive to treatment.

Opposite Models of Expression of Androgen Receptor (AR) and Retinoic Acid Receptor-α (RAR-α) in the Onset of Male Germ Cell Development in Hormonally Manipulated Rats

ABSTRACT Vitamin A together with testosterone (T) and FSH play an essential role in regulating spermatogenesis. Androgens and Vitamin A act through specific nuclear receptors: AR, retinoic acid receptors (RAR-α, β, γ). Present study aimed to investigate relationship between expression of RAR-α and AR in the initiation of spermatogenesis during puberty in conditions of neonatal hormonal manipulation. Experimental model of neonatal treatment with diethylstilbestrol (DES), GnRH-antagonist, T was used. Immunostaining for RAR-α and AR; 121-point counting were applied. Absolute nuclear volume (ANV) was estimated for Sertoli (SC), germ cells (GC) and their subtypes. At onset of puberty (d18) over expression of RAR-α was evident in SCs after DES-10 but not GnRHa treatment. Co-administration of T+DES restored the normal pattern of weak immunoreactivity. An opposite model of expression was seen for AR—loss of expression after DES but not GnRHa application and recovery by T-therapy. Similar reduction was found for spermatogonial ANV in both groups, whereas ANV of spermatocytes (Sc) is reduced in greater extent by DES (10x) than GnRHa (6x). Preleptotene (Pl), leptotene (L) and zygotene (Z) stages was also more affected by DES than GnRHa. Sertoli cell support toward spermatocytes (Sc/SC ratio) was more affected by DES (4x decrease) than GnRHa (2x) and the same tendency is found for Pl/SC and L-Z/SC. In conclusion, data suggest possible interplay between retinoid and androgen signaling in Sertoli cells in the differentiation of male germ cells. The anti-androgenic effect of estrogens on meiotic germ cells is probably mediated by augmentation of RAR- α expression.

Quantification of Rat Spermatogenesis in Late Puberty after Neonatal Hormonal Manipulation

ABSTRACT It has been known for many years that estrogens administration to experimental animals during the neonatal period or adulthood can impair sperm production and maturation. In earlier studies the negative effects of E were explained only as a result of suppression of gonadotropin secretion during the treatment. We aimed to assess GC development on day 35 (different GC types) in tandem with Sertoli cell support toward GCs (efficiency of spermatogenesis) by complex systems of quantitative criteria. We used experimental model for manipulation of neonatal hormonal environment by treatment with DES-10 μg, DES-1 μg, DES-0.1 μg or GnRHa. DES-10 greatly affected testis development and spermatogenesis in rat whereas GnRHa was quite less effective in producing negative impact. In contrast during the onset of puberty (d 18) both treatments exerted similar negative effect, and this time dependent response of the testis corresponds to different hormonal profiles. Quantitative evaluation of late pubertal spermatogenesis demonstrate that the most differentiated GC population- spermatides was the most sensitive to hormonal manipulation compared to spermatogonia (Sg) and spermatocytes (Sc). Different mechanisms are probably involved in mediation of the effect of E and gonadotropins and direct E action on GC differentiation is suggested. Our finding would elucidate our understanding about the hormonal regulation of different germ sell steps of spermatogenesis.