Toxicity In Female Mice Research Articles

Therapeutic Effect of Essential Oils (Citrus sinensis) against Ehrlich Ascites Model Induced Renal Toxicity in Female Mice

Background: Cancer is one of the most dangerous diseases of the twentieth century and the speed of its spread is horrific. It is characterized by cellular growth and invades all tissues of the body. In recent years, all countries of the world have turned to cancer research in order to identify new drugs to treat cancer from various sources , Cancer is the most common disease that causes death in the world and this is attributed to many pathological factors, such as reactive oxygen species, which contribute to the initiation, spread and development of cancer. Methods: Our current research aims to investigate the therapeutic role of essential oils (C.S.) against Ehrlich Tumor renal damage in Mice. The mice were divided into four group (Gp1, control group, Gp2, Essential oils (C.S) group, Gp3, EAC group, Gp4, EAC with Essential oils (C.S). Result: Results showed the Essential oils (C.S) in pretreated (G4) lead to an improvement in urea, creatinine levels when compared to the EAC group. Through our results, it was shown that treatment with essential oils (C.S.) improved the levels of urea and creatinine comparing to the Gp3. It was noted that treatment with essential oils (C.S.) improved kidney tissue and VEGF protein expression the Gp4 compared to the Gp3 Groups. It could be concluded that essential oils (C.S) has a possible benefit to the kidneys against EAC induce kidney Toxicity.

Chamomile Extract Reduces Cardiac Toxicity in Female Mice with Ehrlich Solid Carcinoma.

Cancer is the most serious disorder that may affect a person and is also the leading cause of mortality. Worldwide, breast cancer continues to be the leading cause of cancer-related deaths in women. The popularity of treating diseases using alternative and complementary medicines has increased in recent decades; many of these are derived from plants. Chamomile has a beneficial effect in treating many diseases, there for the purpose of this work is to study how chamomile protect against cardiac damage and toxicity brought on by Ehrlich solid tumor (EST) in adult female mice. 40 female mice were distributed in 4 groups (control, chamomile, EST, EST+chamomile). The research results indicated that EST caused significant alterations in cardiac function and structure. EST induced a significant elevation in serum creatine kinase (CK), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and myoglobin (MB), potassium, chloride ions, cholesterol, triglycerides, low-density lipoprotein (LDL), cardiac tissue damage, apoptotic P53 and Caspase 3 expressions while levels of sodium ions and high-density lipoprotein (HDL) were significantly decreased. Treatments of EST with chamomile improved the biochemical, histopathological, and Immunohistochemical alterations. This suggests that chamomile may be useful as an adjuvant for the treatment and prevention of cardiac toxicity.

Lactating exposure to microplastics at the dose of infants ingested during artificial feeding induced reproductive toxicity in female mice and their offspring

Microplastics (MPs) pollution poses a global environmental challenge with significant concerns regarding its potential impact on human health. Toxicological investigations have revealed multi-system impairments caused by MPs in various organisms. However, the specific reproductive hazards in human contexts remain elusive, and understanding the transgenerational reproductive toxicity of MPs remains limited. This study delves into the reproductive toxicity resulting from lactational exposure to polystyrene MPs (PS-MPs) in female mice, extending the inquiry to assess the reproductive effects on their offspring bred by rigorous natural mating. The MPs dosage corresponds to the detected concentration in infant formula prepared using plastic bottles. By systematically evaluating the reproductive phenotypes of F0 female mice from birth to adulthood, we found that female mice exposed to PS-MPs exhibited delayed puberty, disturbed estrous cyclicity, diminished fertility, elevated testosterone, abnormal follicle development, disrupted ovarian steroidogenesis, and ovarian inflammation. Importantly, the observed inheritable reproductive toxicity manifested with gender specificity, showcasing more pronounced abnormalities in male offspring. Specifically, reproductive disorders did not manifest in female offspring; however, a significant decrease in sperm count and viability was observed in PS-MPs-exposed F1 males. Testicular transcriptomics analysis of F1 males significantly enriched pathways associated with reproductive system development and epigenetic modification, such as male germ cell proliferation, DNA methylation, and histone modification. In summary, real-life exposure to PS-MPs impaired the reproductive function of female mice and threateningly disrupted the spermatogenesis of their F1 male offspring, which raises serious concerns about inter- and trans-generational reproductive toxicities of MPs in mammals. These findings underscore the potential threats of MPs to human reproductive health, emphasizing the need for continued vigilance and research in this critical area.

The antioxidant protective effect of resveratrol on long-term exposure to acrylamide-induced skeletal toxicity in female mice.

Acrylamide (AA) is a toxic substance formed when cooking starch-based foods at high temperatures. Studies have shown that AA can cause neurotoxicity, reproductive toxicity and so on. However, there remains limited understanding of the potential skeletal toxicity of AA. The aim of this study was to investigate the potential skeletal toxicity of AA, as well as the potential bone protective effects of Resveratrol (RVT). Based on the daily intake of adult women, adult female mice was treated with AA at 0, 0.01, 0.1, 1 mg/kg/d or AA/RVT (1 mg/kg/d AA +10 mg/kg/d RVT) for 8 weeks, and skeletal toxicity were evaluated by RT-qPCR and histopathological techniques. The results found that exposure to AA (0.1 or 1 mg/kg/d) after 8 weeks, osteogenesis exhibited pathological damage characteristics such as inhibition of growth plate function, and reduction of fibrous tissue, and cartilage exhibited pathological damage characteristics such as irregular cell morphology and arrangement, and damage to the tidal line. The results of cellular functional gene testing showed a decrease in the expression of functional genes in osteoblasts and chondrocytes. Meanwhile, after further co-treatment with AA (1 mg/kg/d) and resveratrol (RVT) (10 mg/kg/d), we found that RVT restored AA-induced damage to osteogenesis and cartilage, and reduced the high apoptosis and oxidative stress levels in osteogenesis/cartilage after AA exposure. In summary, this study confirmed the skeletal toxicity of AA on female adult mice, and further clarified the antioxidant protective effect of RVT on this toxicity.

Impact of Chia (Salvia hispanica) Seeds Extract on Ehrlich Ascites Model Induced Kidney Toxicity in Female Mice

Background: Ehrlich ascites carcinoma (EAC) is an undifferentiated carcinoma of the breast that was initially hyperdiploid, 100% malignantand had a short life span. It also had a high transplantability rate, no recurrence and rapid dissemination. Methods: Therefore, our study designed to assess the potential ameliorative ability of Chia (Salvia hispanica) seeds extract (CSE) on Ehrlich ascites carcinoma (EAC) induced kidney toxicity and tissue damage in mice. Forty female Swiss albino mice in all were split equally into four teams (Gp1, control; Gp2, CSE; Gp3, EAC; Gp4, EAC+CSE). Result: Current results revealed that; EAC induced elevated in the levels of serum urea, creatinine, potassium ions, chloride ions, renal tissue injury and a significant depletion in serum sodium ions, calcium ions as compared to normal control. In addition to EAC induced variable pathological changes in glomeruli and renal tubules as a marked renal damage, marked degeneration in renal tissues, moderate glomerular atrophyand marked cellular infiltration. Treatment of EAC with CSE (EAC+CSE) improved kidney functions and structure against EAC; where depletion take place in the levels of serum urea, creatinine, potassium ions, chloride ions and elevation in the levels of sodium ions, calcium ions as compared to EAC. One may draw the conclusion that CSE Having the ability to protect the kidneys from EAC cells induced kidney toxicity.

TiO2 nanoparticles combined with polystyrene nanoplastics aggravated reproductive toxicity in female mice via exacerbating intestinal barrier disruption.

TiO2 nanoparticles (NPs), a widely used food additive in the food industry, have been shown to aggravate the progress of metabolic diseases. Nanoplastics (NPLs) are an emerging contaminant widely present in the food system and have been shown to induce ovarian disorders in mammals. Noteworthy, they can be ingested by humans through "contaminated" food, while the potential toxicity of NPLs and TiO2 NPs combined remains unclear. In this work, we investigated the potential effects and mechanisms of co-exposure to polystyrene (PS) NPLs and TiO2 NPs on the ovary in female mice. Our results revealed that the co-exposure of TiO2 NPs and PS NPLs caused significant injury to ovarian structure and function, but individual exposure had no effect. Moreover, compared to the TiO2 NPs group, co-exposure aggravated the intestinal barrier damage in mice, increasing the bioaccumulation of TiO2 NPs in the ovary. After being supplemented with the oxidative stress inhibitor N-acetyl-L-cysteine, the expression of ovarian antioxidant genes increased, and the ovarian structural and functional injury in co-exposure mice reverted to normal levels. This study demonstrated that co-exposure to PS NPLs and TiO2 NPs can cause more severe female reproductive dysfunction and deepened the toxicological insights between NPLs and NPs. This article is protected by copyright. All rights reserved.

The hypoglycemic and anti-hyperlipidemic activity of vitamin C in di(2-ethylhexyl) phthalate-induced toxicity in female mice, Mus musculus

The hypoglycemic and anti-hyperlipidemic activity of vitamin C in di(2-ethylhexyl) phthalate-induced toxicity in female mice, Mus musculus

Oleuropein suppresses endometriosis progression and improves the fertility of mice with endometriosis

BackgroundEndometriosis is an estrogen-dependent inflammatory reproductive disease. Therefore, systematic estrogen depletion and anti-inflammatory drugs are the current treatment for endometriosis. However, current endometriosis treatments have low efficacy and cause adverse effects in endometriosis patients. Consequently, alternative endometriosis treatments targeting endometriosis-specific factors are in demand. In this context, ERβ was selected as a druggable target for endometriosis due to its critical role in progression. Therefore, selective targeting of ERβ without inhibiting ERα activity would be a new paradigm for endometriosis treatment to overcome the low efficacy and adverse effects of hormonal endometriosis therapy.MethodsCell-based ERβ and ERα activity assay systems were employed to define a selective ERβ-inhibiting chemical product from a library of natural products. A surgically induced endometriosis mouse model was used to determine whether an ERβ inhibitory drug suppressed endometriosis progression. Mice with endometriosis were randomly separated and then orally treated with vehicle or 25 mg/kg oleuropein (once a day for 21 days), an ERβ inhibitory drug. The volume of endometriotic lesions or luciferase activity of endometriotic lesions was examined to define the growth of ectopic lesions in mice with endometriosis. The metabolite and levels of metabolic enzymes of the liver and kidney were determined in the serum of female mice treated with vehicle and oleuropein (25 mg/kg, once a day for 21 days) to define the toxicity of oleuropein. The in vitro decidualization assay was conducted with normal human endometrial stromal cells and endometriotic stromal cells to determine whether oleuropein overcomes decidualization in endometriosis patients. The pregnancy rate and pup numbers of C57BL/6 J female mice with endometriosis treated with vehicle or oleuropein (n = 10/group) were determined after mating with male mice. The cytokine profile in endometriotic lesions treated with vehicle and oleuropein (25 mg/kg) was determined with a Mouse Cytokine Array Kit.ResultsAmong natural products, oleuropein selectively inhibited ERβ but not ERα activity in vitro. Oleuropein treatment inhibited the nuclear localization of ERβ in human endometrial cells upon estradiol treatment. Oleuropein (25 mg/kg) treatment suppressed the growth of mouse (6.6-fold) and human (sixfold) ectopic lesions in mice with endometriosis compared to the vehicle by inhibiting proliferation and activating apoptosis in endometriotic lesions. Oleuropein treatment did not cause reproductive toxicity in female mice. Additionally, mice with endometriosis subjected to oleuropein treatment had a higher pregnancy rate (100%) than vehicle-treated mice (70%). Furthermore, oleuropein treatment partially recovered the decidualization impact of human endometriotic stromal cells from endometriotic lesions compared to the vehicle. Oleuropein-treated mice with endometriosis exhibited significantly lower levels of cytokines directly regulated by ERβ in ectopic lesions than vehicle-treated mice, illustrating the improvement in the hyperinflammatory state of mice with endometriosis.ConclusionsOleuropein is a promising and novel nutraceutical product for nonhormonal therapy of endometriosis because it selectively inhibits ERβ, but not ERα, to suppress endometriosis progression and improve the fertility of mice with endometriosis.

Curative Potentials of Garlic (Allium sativum) Extract against Di-(2-Ethylhexyl) Phthalate Induced Reproductive Toxicity in Female Mice

The present study was intended to find out the curative potentials of Garlic (Allium sativum) against di-(2-Ethylhexyl) phthalate (DEHP) induced toxicity in the reproductive system of female mice. Forty female mice were divided into four groups (n=10) as the (a) control group was given normal feed and drinking water, (b) aqueous garlic extract treated group (500 mg/kg), (c) DEHP group received 500 mg/kg in corn oil, and (d) DEHP + aqueous garlic extract each at a dosage of 500 mg/kg body weight. All treatments were given daily through oral gavage for 28 days. After completion of the experiment, all the animals were dissected through cervical dislocation to get reproductive organs. Collected organs were weighed and processed through the conventional histology technique of staining with eosin and hematoxylin. This study indicated that DEHP exposure caused a significant decrease (P<0.001) in body weight and weight of the complete female reproductive tract as compared to the control group, while the garlic co-administered group showed prominent improvement in body and organ weight when compared to only DEHP treatment. The adverse effect of DEHP on the histology of the ovary such as a decreased mean number of developing follicles, thin and irregular corona radiata, disruption of cumulus oophorus, and reduction in the size of the antral cavity of the tertiary follicle was observed. However, a significant recovery in the development of follicles was seen in DEHP plus garlic-treated group. DEHP plus garlic extract treatment showed protective effects on the uterus, such as a significant increase in the diameter of the uterus (P<0.001), muscularis, mean number of endometrial glands (P<0.001), and endometrial epithelial heights as compared to only DEHP exposed group. Hence, garlic extract showed significant ameliorative potential against DEHP-induced reproductive anomalies in female mice.

Co-exposure to polystyrene microplastics and lead aggravated ovarian toxicity in female mice via the PERK/eIF2α signaling pathway

Generally, individual microplastics (MPs) or lead (Pb) exposure could initiate ovarian toxicity. However, their combined effects on the ovary and its mechanism in mammals remained unclear. Female C57BL/6 mice were used in this study to investigate the combined ovarian toxicity of polystyrene MPs (PS-MPs, 0.1 mg/d/mouse) and Pb (1 g/L) for 28 days. Results showed that co-exposure to PS-MPs and Pb increased the accumulation of Pb in ovaries, the histopathological damage in ovaries and uterus, the serum malondialdehyde levels and decreased serum superoxide dismutase and sex hormone levels significantly when compared with single PS-MPs and Pb exposure. These observations indicated that co-exposure exerted more severe toxicity to mouse ovaries and uterus. Furthermore, co-exposure to PS-MPs and Pb caused endoplasmic reticulum (ER) stress by activating the PERK/eIF2α signaling pathway in the ovary, which resulted in apoptosis. However, the oxidative and ovarian damage were alleviated, and the mRNA levels of genes related to the PERK/eIF2α signaling pathway were down-regulated to levels of the control mice in the PS-MPs and Pb co-exposed mice administered with ER stress inhibitor (Salubrinal, Sal) or the antioxidant (N-acetyl-cysteine, NAC). In conclusion, our findings suggested that the combination of PS-MPs and Pb aggravated ovarian toxicity in mice by inducing oxidative stress and activating the PERK/eIF2α signaling pathway, thereby providing a basis for future studies into the combined toxic mechanism of PS-MPs and Pb in mammals.

Sexual dimorphism in gut microbiota dictates therapeutic efficacy of intravenous immunoglobulin on radiotherapy complications

IntroductionWith the mounting number of cancer survivors, the complications following cancer treatment become novel conundrums and starve for countermeasures. Intravenous immunoglobulin (IVIg) is a purified preparation for immune-deficient and autoimmune conditions. ObjectivesHere, we investigated whether IVIg could be employed to fight against radiation injuries and explored the underlying mechanism. MethodsHematopoietic or gastrointestinal (GI) tract toxicity was induced by total body or abdominal local irradiation. High-throughput sequencing was performed to analyze the gut microbiota configurations and gene expression profile of small intestine. The untargeted metabolomics of gut microbiome was assessed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analyses. Hydrodynamic-based gene delivery was used to knockdown the target genes in vivo. ResultsIntravenous injection of IVIg protected against radiation-induced hematopoietic and GI tract toxicity in female mice but not in males. IVIg structured sex-characteristic gut microbiota configurations in abdominal irradiated mice. The irradiation enriched gut Lachnospiraceae in female mice but reduced those in males. IVIg injection combined with oral gavage of Lachnospiraceae or its metabolite hypoxanthine, alleviated radiation toxicity in male mice however, Lachnospiraceae or hypoxanthine alone failed to ameliorate the injuries. Abdominal local irradiation drove sex-distinct gene expression signatures in small intestine. Mechanistic investigation showed that replenishment of Lachnospiraceae or hypoxanthine offset abdominal radiation-reduced PLD1 expression in male mice. In females, irradiation elevated PLD1 expression. Deletion of PLD1 in GI tract of female mice erased the radioprotective effects of IVIg. ConclusionIVIg battles against radiation injuries in a sex-specific, gut microbiome-dependent way through Lachnospiraceae/hypoxanthine/PLD1 axis. Our findings provide a sex-precise therapeutic avenue to improve the prognosis of cancer patients with radiotherapy in pre-clinical settings.

Rosmarinic acid relieves cisplatin-induced ovary toxicity in female mice via suppression of oxidative stress and inflammation.

Rosmarinic acid having potential anti-inflammatory and free radical scavenging activity. We examined the chemotherapeutic effect of rosmarinic against cisplatin (CIS)-induced ovarian toxicity via modulation of oxidative stress and inflammation. Swiss BALB mice used in experimental protocol and mice were divided into different groups. Intraperitoneal injection of CIS (7 mg/kg) was used for ovarian cancer induction. The rats were received rosmarinic acid (2.5, 5, and 10 mg/kg, body weight) treatment for 22 weeks. Body weight, ovary weight food, and water intake were estimated at regular time intervals. Hormonal and antioxidant parameters were estimated in the ovary tissue and serum at the end of the study. Cytokines, inflammatory, and apoptosis parameters were determined at the end of the study. Finally, the ovary tissue histopathology was performed at end of the experimental study. Rosmarinic acid significantly (p < 0.001) improved the body weight and reduced the ovary weight. Rosmarinic acid considerably reduced the hormonal assay parameters, such as antimullerian hormone,estradiol, luteinizing hormone,and follicle-stimulating hormonecompared to model control mice. Rosmarinic treatment significantly (p < 0.001) reduced the level of nitric oxide, myeloperoxidase, and boosted the level of antioxidant parameters, such as glutathione, superoxide dismutase, catalase,and glutathione peroxidaseinserum and ovary tissue. Rosmarinic acid downregulated the cytokines like interleukin-6, tumor necrosis factor-α, interleukin-1β; inflammatory parameter includes prostaglandin E2 , cyclooxygenase-2,and inducible nitric oxide synthaseat a dose-dependently. Ovary tissue histopathology showed improvement after rosmarinic acid treatment. The result suggests that rosmarinic acid is a protective effect in ameliorating CIS-induced ovary toxicity via alteration of inflammatory and apoptosis parameters.

Aqueous wood-ash extract of Parkia biglobosa causes reproductive toxicity in female mice

Aqueous wood-ash extract of Parkia biglobosa causes reproductive toxicity in female mice

Oceanapia magna Sponge Presents Dual Effect on the Gastrointestinal Motility of Rodents: In Vitro and In Vivo Assays.

Oceanapia magna Santos-Neto, Nascimento, Cavalcanti and Pinheiro sponges are distributed across tropical worldwide seas. Some studies of marine products have shown interesting activities in smooth muscle models. Hence, we assessed the effect of the ethanolic extract of Oceanapia magna. (OC-EtOH) on acute toxicity and gastrointestinal motility (in vitro and in vivo) in rodent models. On guinea pig ileum, OC-EtOH induced a concentration dependent contraction on basal tonus, which was not inhibited by atropine, but in the presence of pyrilamine or verapamil, the effect was antagonized. Contrastingly, on KCl- or histamine-induced contractions, OC-EtOH presented a transient contraction followed by a concentration-dependent relaxation. Moreover, OC-EtOH presented a relaxant profile on cumulative curves to CaCl2 and tonic contraction induced by S-(-)-BayK8644, through Cav blockade. The acute toxicity assay showed that OC-EtOH (2,000 mg/kg, p.o.) did not present any sign of toxicity in female mice. Additionally, OC-EtOH presented antidiarrheal effect in mice, increased the intestinal normal transit and reduced the castor oil-induced intestinal transit. Thus, OC-EtOH presented a dual effect on guinea pig ileum promoting contraction through activation of H1 and CaV, and relaxation through CaV blockade, besides the effect on upper gastrointestinal transit in mice, showing a potential medicinal use of this sponge in intestinal diseases such as diarrhea.

Ameliorative effects of vitamin B17 on the kidney against Ehrlich ascites carcinoma induced renal toxicity in mice.

Cancer is the major cause of death and many factors that lead to its occurrences, such as environmental pollution and pesticides and other factors. Ehrlich carcinoma development depends on many things associated with the environment, nutrition, personal habits, and family history. The present study aimed to evaluate the potential protective effects of vitamin B17 (VB17) against Ehrlich ascites carcinoma (EAC) that induced kidney toxicity in female mice. The mice were divided into five groups (first group, control group; second group, VB17 group; third group, EAC group; fourth group, pretreated EAC with VB17; fifth group, cotreated EAC with VB17). Results showed the VB17 in pretreated (G4) and cotreated (G5) groups lead to an improvement in DNA damage and cytological examination, in addition significantly (P < .05) increase in Na+ , red blood cell, hemoglobin, hematocrit value, mean corpuscular hemoglobin (MCH), and MCH concentration, whereas significantly (P < .05) decrease in urea, creatinine, K+ , platelets, and white blood cells while insignificant (P < .05) changes in mean corpuscular volume when compared to the EAC group. Many histopathological changes were observed in kidney sections in EAC as marked damage and degenerated, glomerular atrophy, the Malpighian corpuscles that lost their characteristic configuration. On the other hand, a moderate improvement and arrangement in the kidney histological structure in pretreated VB17 + EAC, while a mild enhancement and arrangement of the kidney structure in cotreated EAC + VB17. In addition, depletion in renal P53 and PCNA protein expression compared with the EAC group. It could be concluded that VB17 has a potential renal protective effect against EAC cells induced kidney injury.

Acute and Subacute Toxicity Evaluation of Alkaloids of Peganum harmala L. in Experimental Mice

The objective of the study was to evaluate the acute and subacute toxicity of total alkaloids seeds of Peganum harmala in female mice. All morphological, biochemical, hematological, histopathological changes, in addition to mortality and bodyweight changes were recorded. After acute intraperitoneal administration of dose118 mg/kg, there were no any remarkable changes in general appearance and mortality. After 24h, a significant increase in relative weights of heart and brain with no change in hematological, biochemical parameter compared to the normal group. For 5 days a significant reduction in the relative weights of the kidneys and increase of brain with significant change in hematological (MCHC, MCV) and biochemical parameter (AST, ALP and Urea). Subacute study of dose (18 mg/kg) for 28 days showed no remarkable changes in general appearance and deaths occurred in experimental group. A significant increase in relative weight of brain compared to the normal group was observed. In biochemical parameters, a significant increase was seen in both ALT and AST enzyme activities. There was no significant change in hematological parameters. Histopathological examination revealed a ground glass appearance of hepatocytes and the vascular congestion. Alkaloids seeds of P.harmala showed significant toxicity in female mice.

Anti-inflammatory and toxicological evaluation of essential oil from Piper glabratum leaves

Ethnopharmacological relevanceAlthough some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited. Aim of the studyThis study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice. Materials and MethodsThe acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight. In the subacute toxicity test, the females received 500 or 1000mg/kg/body weight of OEPG for 28 days. The anti-inflammatory potential of OEPG was evaluated using four models including pleurisy, edema, mechanical hyperalgesia and cold allodynia models in mouse paws. ResultsNo clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD50 is greater than 5000mg/kg. The subacute exposure to OEPG produced no significant changes in the hematological or biochemical parameters. Similarly, the histology of the organs and the estrus cycle displayed no marked alterations. OEPG exhibited anti-inflammatory activity as indicated by inhibition of the leukocyte migration (100, 300, 700mg/kg) and the protein extravasation into the pleural exudates (700mg/kg). After intraplantar injection of carrageenan, it was observed that the 700mg/kg dose of OEPG reduced edema formation and decreased the sensitivity to mechanical stimulation and cold. ConclusionsThese results demonstrate the anti-inflammatory potential of the essential oil of P. glabratum leaves in the absence of toxicity in female mice.

Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice.

Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals.

The reproductive toxicity of saponins isolated from Cortex Albiziae in female mice

Saponin frsom Cortex Albiziae (SCA) are extensively used in the clinical treatment of tumor and depression. However, SCA may cause several adverse effects, including reproductive toxicity. The present study was designed to assess the mechanism by which SCA cause reproductive toxicity in female mice. The general reproductive toxicity testing was accomplished in female Kunming mice. The animals were divided into four groups: three groups that were treated by oral gavage with 135, 270, and 540 mg·kg−1·d−1 of SCA prepared in physiological saline, respectively, and one vehicle control group that was treated with physiological saline only. The gestational toxicity tests were conducted at 540 mg·kg−1·d−1. The general reproductive toxicity results showed that the pregnancy rate of the SCA-treated group decreased with the pregnancy rate being decreased by 70% at 540 mg·kg−1·d−1. SCA elicited maternal toxicity in the ovary and the uterus, but no fetal toxicity or teratogenicity was observed. The rates of implantation in the early, middle, and late pregnancy were all decreased, with stillbirths and maternal deaths being observed. Histopathological changes showed that SCA adversely affected the ovary and the uterus. In conclusion, SCA-induced reproductive toxicity in female mice is most likely caused by its damage to the ovary and the uterus.

Oxidative stress and ER stress induce Zidovudine (AZT)‐mediated hepatic lipid accumulation

Zidovudine (AZT) was the first drug approved by the U.S. Food and Drug Administration for treating AIDS patients. The clinical effectiveness of AZT is constrained due to its various adverse side effects including hepatotoxicity. However, the mechanism of hepatic lipid accumulation in AZT‐treated individuals is unknown. We hypothesized that AZT‐induced oxidative stress alters the mitochondrial fat oxidation pathway, leading to fat accumulation. Our study showed significant increase in lipid accumulation, inflammation and toxicity in female mice exposed to AZT for 10 days. Markers of oxidative stress such as CYP4A levels, protein oxidation, nitration, glycation and lipid peroxidation were significantly higher in the AZT‐treated mice as compared to the controls. Further, the levels of ER stress marker proteins like GRP78, p‐PERK, and p‐ELF2α were significantly elevated in AZT‐treated mice. In addition, significantly increased levels of nuclear SREBP‐1c and acetyl‐CoA carboxylase along with significant decrease in the levels of phospho‐AMP kinase and PPARα, a key transcription factor for fatty acid oxidation, were observed in AZT‐treated group. Collectively, these data indicate that oxidative stress and ER stress play a critical role in lipid accumulation and hepatotoxicity in AZT‐treated animals. [Support: Intramural Research Program of NIAAA].