Prenatal exposure to ethion caused maternal and foetal toxicity in rats.

Ethion is a class II moderately toxic organothiophosphate pesticide. The main objective of this study was to evaluate the maternal and foetal toxicity of ethion in rats. Pregnant rats were divided into 5 groups. Group I served as control. Group II, III, IV, and V were orally administered with 0.86, 1.71, 3.43, and 6.9 mg/kg of ethion respectively, from gestational day (GD) 6-19. Dams were sacrificed on GD 20. Maternal toxicity was assessed by body weight gain, foetal resorptions, oxidative stress, liver and kidney function tests, and histopathology. Foetal toxicity was assessed by physical status, gross, teratological and histopathological examination. Ethion caused dose-dependent reduction in maternal body weight gain, increased resorptions, and reduced gravid uterine weights. Elevated MDA levels and altered levels of GSH, SOD and catalase were recorded in pregnant dam serum and tissues. SGOT, SGPT, total bilirubin, urea, uric acid, and creatinine were elevated in ethion groups indicating liver and kidney toxicity. Histology of uterus revealed myometrial degeneration and mucosal gland atrophy in uterus of pregnant dams and degenerative changes in placenta. It showed histological alterations in liver, kidney, and lungs. There was reduction in the foetal body weights and placental weights, and degenerative changes in the foetal liver and kidney. Gross evaluation of foetuses showed subcutaneous hematoma. Skeletal evaluation showed partial ossification of skull bones, costal separation, and agenesis of tail vertebrae, sternebrae, metacarpals and metatarsals. The findings reveal that prenatal exposure to ethion caused maternal and foetal toxicity in rats.

Nano-quercetin mitigates triazophos-induced testicular toxicity in rats by suppressing oxidative stress and apoptosis.

The present study was designed to evaluate the testicular toxicity of triazophos in rats and to check the ameliorative effect of nano-quercetin against triazophos-induced toxicity. Nano-quercetin was synthesized from quercetin and characterized. Male Wistar rats were divided into seven groups. The control group received olive oil as a vehicle orally. The high-dose triazophos group and the low-dose triazophos group received 1/10th LD50 of triazophos (7.6 mg/kg) and 1/20th LD50 of triazophos (3.8 mg/kg), respectively. Two groups of animals were dosed with quercetin and nano-quercetin, both at 50 mg/kg body weight orally. The final two groups received high-dose triazophos with co-administration of quercetin and nano-quercetin, respectively. Triazophos disrupted the male endocrine axis by reducing the levels of steroidogenic enzymes 3-ß-HSD and 17-ß-HSD in testicular cells, further reducing FSH and testosterone. Also, triazophos increased the reactive oxygen species, induced lipid peroxidation, decreased the mitochondrial membrane potential, and elevated the number of apoptotic cells in rat testes. Nano-quercetin ameliorated the testicular oxidative stress and apoptotic and endocrine parameters more efficiently than quercetin. Besides, nano-quercetin alleviated the histopathological and biochemical alterations of triazophos. It is concluded that nano-quercetin has higher anti-oxidant efficacy than quercetin in protecting rats against triazophos-induced testicular toxicity.

Differential Expression of Prostaglandin Receptors in Canine Uterus With Pyometra.

The objective of the study was to ascertain the role of prostaglandins Viz., PGE2 and PGF2α, and their respective receptors in the pathophysiology of canine pyometra. Normal (n = 6) and pyometra (n = 8) affected uterus were collected from bitches undergoing ovariohysterectomy. Pyometra was graded according to histopathological alterations. The levels of PGE2 and PGF2α were estimated in the endometrium. The differential expression in the mRNA of PGF2α receptor (FP) and PGE2 receptors (EP1, EP2, EP3, and EP4) were studied in the endometrium and myometrium of the pyometra-affected uterus. Normal uterus served as calibrator. Elevation of both PGE2 and PGF2α levels in the endometrium of pyometra-affected bitches was observed. The FP receptor gene in the endometrium and myometrium of pyometra-affected bitches was downregulated (P < .05). Out of all EP receptors, only EP2 receptor has shown upregulation in both endometrium and myometrium of pyometra affected uterus. EP3 receptor got downregulated in both endometrium and myometrium in pyometra. Thus, downregulation of FP, EP3 receptors in the myometrium reinforces the lack of contractility in pyometra-affected bitches favoring bacterial proliferation and subsequent pus accumulation. Moreover, upregulation of EP2 receptors in the pyometra bitches suggests the scope of selective pharmacological inhibition of EP2 receptors as an adjunct therapy in the treatment of pyometra.

Studies on oral subacute toxicity of cartap in male mice.

S-[3-carbamoylsulfanyl-2-(dimethylamino)propyl] carbamothioate (Cartap) (CAS number: 15263-52-2) is a synthetic insecticide of thiocarbamates group that is extensively used in field of agriculture for controlling of several pests like rice stem borer, leaf folder pests in paddy field and diamond back moth, aphids in cabbage and cauliflower crops. Cartap, as a pesticide has not been investigated yet for its effect on vital organs and biochemical stress in vivo and the present study was undertaken to evaluate the same in Swiss albino mice. For this purpose male mice were given three different dose levels of cartap, i.e. 5 mg/kg, 7.5 mg/kg and 15 mg/kg body weight respectively, for 28 days orally. Water was used as vehicle to dissolve cartap. Oral administration of cartap caused significant increase in serum biomarkers, tissue oxidants and decrease in antioxidants along with histopathological findings in liver, kidney and brain tissues. Thus, present study showed that in vivo exposure to cartap induces tissue damage probably via oxidative stress in important vital organs of mice.

Casein kinase 2 inhibition impairs spontaneous and oxytocin-induced contractions in late pregnant mouse uterus.

NEW FINDINGS: What is the central question of this study? Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility? What is the main finding and its importance? Inhibition of CK2 impaired the spontaneous and oxytocin-induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin-induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics. ABSTRACT: The protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin-induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX-4945 elicited a concentration-dependent relaxation in late pregnant mouse uterus. CX-4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin-induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F2α response, but CX-4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin-induced uterine contractions in the late pregnant mouse.

Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse.

High cholesterol is known to negatively affect uterine contractility in ex vivo conditions. The aim of the present study was to reveal the effect of in vivo hypercholesterolemia on spontaneous and oxytocin-induced uterine contractility in late pregnant mouse uterus. Female Swiss albino mice were fed with high cholesterol (HC) diet (0.5% sodium cholate, 1.25% cholesterol and 15% fat) for 6 weeks and then throughout the gestation period after mating. On day 19 of gestation, serum cholesterol level was increased more than 3-fold while triglycerides level was reduced in HC diet-fed animals as compared to control animals fed with a standard diet. In tension experiments, neither the mean integral tension of spontaneous contractility nor the response to CaCl2 in high K+-depolarized tissues was altered, but the oxytocin-induced concentration-dependent contractile response in uterine strips was attenuated in hypercholesterolemic mice as compared to control. Similarly, hypercholesterolemia dampened concentration-dependent uterine contractions elicited by a GNAQ protein activator, Pasteurella multocida toxin. However, it had no effect on endogenous oxytocin level either in plasma or in uterine tissue. It also did not affect the prostaglandin release in oxytocin-stimulated tissues. Western blot data showed a significant increase in caveolin-1 and GRK6 proteins but decline in oxytocin receptor, GNAQ and RHOA protein expressions in hypercholesterolemic mouse uterus. The results of the present study suggest that hypercholesterolemia may attenuate the uterotonic action of oxytocin in late pregnancy by causing downregulation of oxytocin receptors and suppressing the signaling efficacy through GNAQ and RHOA proteins.

Betulinic acid attenuates renal fibrosis in rat chronic kidney disease model.

BACKGROUND: Most chronic kidney diseases (CKDs), regardless of the nature of the initial injury, progress to end-stage renal disease (ESRD) characterized by fibrosis with irreversible loss of tissue and function. Thus, improved and more effective therapies are critical. Betulinic acid (BA), a pentacyclic triterpene is a compound in the pipeline of anti-cancer drug development. It has been shown to a possess variety of beneficial effects in many disease conditions. However, its efficacy against CKD is yet to be explored. OBJECTIVE: The present study was undertaken to investigate the effect of BA on renal fibrosis in the rat model of adenine-induced CKD. RESULTS: CKD rats gained significantly less weight during the experimental period when compared to control rats and BA treatment did not significantly increase the weight gain in CKD rats. CKD rats showed elevated levels of serum blood urea nitrogen (BUN), creatinine and uric acid along with increased levels of kidney injury markers such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Further, in comparison to control rats, kidney samples from CKD rats revealed increased profibrotic protein levels like transforming growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), fibronectin, collagen type I and hydroxyproline indicating a progressive fibrotic response. These data are further fortified by histological findings where kidney damage and fibrosis are clearly evident as dilatation of tubules, glomerular degeneration and vacuolation along with deposition of collagen fibers. However, the above-mentioned findings in CKD rats were significantly reversed by BA-treatment revealing its nephroprotective potential and anti-fibrotic activity. CONCLUSION: The biochemical mechanism of the nephroprotective and anti-fibrotic effect of BA in the adenine-induced CKD rats might be mediated by inhibition of pro-fibrotic protein production thereby hindering the kidney tissue damage along with improvement in kidney function. Thus, BA could be an adjunct agent to retard fibrosis in CKD subjects.

Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytes in vitro.

Arsenic is a potent environmental pollutant and immunotoxic agent. Curcumin is a natural anti-oxidant used to treat a broad variety of diseases. Here, the effects were investigated of curcumin on sodium arsenite-induced apoptosis in murine splenocytes in vitro. Cells were exposed to sodium arsenite (NaAsO2, 5 µM) with and without curcumin (5 and 10 µg/ml) and incubated at 37°C for 12 h. NaAsO2 caused a decrease in cell viability and induction of apoptosis. These outcomes were concurrent with increases in the numbers of cells with reactive oxygen species generation, loss of mitochondrial transmembrane potential, an increase in the frequency of cells with sub-G1 DNA content, and DNA fragmentation. Co-administration of curcumin with the NaAsO2 caused significant recoveries in cell viability values and mitigation of the induced apoptosis-related molecular changes. A significant protection against apoptosis parameters in murine splenocytes simultaneously treated with NaAsO2 and curcumin suggested a protective efficacy of curcumin. From the results it is concluded that the immuno-modulation exerted by curcumin might be attributed to its multifaceted effects including its anti-oxidative and anti-apoptotic properties. These findings have implications not only for the under-standing of the toxicity of arsenic to murine splenocytes in vitro but are also potentially important for developing preventive and/or corrective strategies against/during chronic arsenicosis.

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats.

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.