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.

Lysophosphatidic acid enhances PGE2 to PGF2α ratio and nitric oxide level in nonpregnant buffalo uterus.

Lysophosphatidic acid (LPA) is a small ubiquitous lipid exerting diverse biological functions. Its role in reproduction in different species has created great interest in recent times. In the present study, we aimed to elucidate LPA signaling in nonpregnant buffalo uterus by in vitro studies. Standard techniques like real-time PCR (for mRNA expression of LPARs and COX-2 and iNOS), Western blot (for PPARγ protein expression), sandwich ELISA (for PGE2 and PGF2α assay) and histopathology (for assessment of endometrial architecture in culture) were used in this study. The buffalo uterine tissues were collected from the local slaughterhouse and were selected for the study on the basis of the presence of corpus luteum on the ovary (n = 5). The LPAR3 receptor was the highest expressed receptor as compared to LPAR1 and LPAR6 in non-pregnant uterine tissues after 6 h incubation in Dulbecco's Modified Eagle Medium (DMEM). 50 µM LPA increased the mRNA expressions of COX-2 and iNOS enzymes which were attenuated by the treatment of LPAR1/3 antagonist Ki16425. PPARγ antagonist GW9662 prevented the LPA-induced increase in iNOS mRNA expression but did not alter the COX-2 expression. LPA also enhanced the PGE2 to PGF2α ratio in uterine tissue homogenates which was inhibited by all the receptor antagonists as well as by the inhibitors of COX-2 and iNOS. LPA also increased the total nitrite level in tissue homogenates in LPAR1/3- and iNOS-dependent manner. Additionally, we demonstrate PPARγ mRNA and protein expressions in nonpregnant buffalo endometrium. In conclusion, the results of the present study suggest that LPA acts as a luteotropic factor during the estrus cycle in nonpregnant buffalo uterus by enhancing PGE2 to PGF2α ratio and NO level through multiple receptors.

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.