Protective effect of alpha­lipoic acid against in utero cytarabine exposure-induced hepatotoxicity in rat female neonates.

Cytarabine, an anti-metabolite drug, remains the mainstay of treatment for hematological malignancies. It causes various toxic effects including teratogenicity. Alpha lipoic acid (ALA) is a natural antioxidant reported to offer protection against hepatotoxicity induced by various pathological conditions, drugs, or chemicals. We investigated the protective effect of ALA against prenatal cytarabine exposure-induced hepatotoxicity in rat female neonates. A total of 30 dams were randomly assigned to five groups and received normal saline, ALA 200 mg/kg, cytarabine 12.5 mg/kg, cytarabine 25 mg/kg, and cytarabine 25 mg/kg + ALA 200 mg/kg, respectively, from gestational day (GD)8 to GD21. Cytarabine and ALA were administered via intraperitoneal and oral (gavage) routes, respectively. On postnatal day (PND)1, all the live female neonates (pups) were collected and weighed. The blood and liver from pups were carefully collected and used for histopathological, and biochemical evaluations. A significant and dose-dependent decrease in maternal food intake and weight gain was observed in the pregnant rats (dams) of the cytarabine groups as compared to the dams of the control group. The pups exposed to cytarabine showed a significant and dose-dependent (a) decrease in body weight, liver weight, hepatosomatic index, catalase, superoxide dismutase, glutathione, glutathione peroxidase, serum albumin levels and (b) increase in malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, AST/ALT ratio, and histopathological anomalies. Maternal co-administration of ALA ameliorated these biochemical changes and histopathological abnormalities by combating oxidative stress. Future studies are warranted to explore the molecular mechanisms involved in the ALA's protective effects against prenatal cytarabine-induced hepatotoxicity.

Maternal supplementation of alpha-lipoic acid ameliorates prenatal cytarabine-induced mutilation in reproductive development and function in F1 male adult rats.

AIMS: Cytarabine (CYT), a prevalent anticancer drug for blood cancers, detrimentally affects male reproductive development and function. Alpha-lipoic acid (ALA), a universal antioxidant, offers defense against chemical-induced reproductive dysfunction. Our study sought to explore ALA's protective role against prenatal CYT-induced reproductive impairment in F1 male adult rats. MAIN METHODS: Pregnant rats were divided into 5 groups and administered normal saline, ALA 200 mg/kg, CYT 12.5 mg/kg, CYT 25 mg/kg, and CYT 25 mg/kg + ALA 200 mg/ kg from gestational day 8 to 21. On postnatal day 73, F1 male rats were sacrificed, and general, oxidative, steroidogenic, spermatogenic, histological, and morphometrical parameters were evaluated. KEY FINDINGS: Prenatal CYT caused dose-dependent reductions in body weight, testis, and accessory gland weights; elevated oxidative stress; delayed puberty onset; sperm anomalies (decreased count, motility, viability, seminal fructose; increased morphological anomalies); impeded steroidogenesis (lower testosterone, follicle-stimulating hormone, luteinizing hormone, 3ß-Hydroxysteroid dehydrogenase(HSD), 17ß-HSD, and elevated cholesterol); and testicular histopathological and morphometric disturbances. Maternal supplementation of ALA was found to alleviate all the CYT-induced reproductive disruptions. SIGNIFICANCE: The present work accentuates the beneficial actions of ALA against CYT-induced impairment in reproductive development and functions by combating disruptions in oxidative balance, steroidogenesis, spermatogenesis, and testicular histological aberrations. However, future experimental and clinical studies are warranted to explore the molecular mechanisms involved in the ALA's protection against prenatal CYT-induced testicular injury.

Severe Ovarian Hyperstimulation Syndrome in a Case of Nonmutated Recurrent Genuine Empty Follicle Syndrome.

Empty follicle syndrome (EFS) is a rare event in which no oocytes are retrieved from apparently normal growing follicles with normal steroidogenesis despite meticulous follicular aspiration in assisted reproductive technology (ART) cycles. EFS is mainly of two types, genuine EFS and false EFS. Here, we report a case of a 24-year-old woman presenting with primary infertility with normal ovarian reserve and regular menstrual cycles, husband having severe "oligo-astheno-teratozoospermia," and planned for ART treatment. We could not retrieve any oocytes in successive cycles despite optimum human chorionic gonadotropin (hCG) levels on the day of oocyte retrieval and using different management protocols mentioned until now in the literature. The whole genomic analysis was found to be normal (46, XX). Further, the patient had experienced severe ovarian hyperstimulation syndrome (OHSS) after the second cycle of ovarian stimulation despite no luteal hCG support. We were ineffectual to find the cause of recurrent EFS in this patient and therefore counseled the patient for donor oocytes. This case highlights the difficulty in treating genuine EFS patients and the need for monitoring serum estradiol levels during ovarian stimulation to prevent another serious complication of OHSS.

Pre-pubertal cyclophosphamide exposure-induced mutilation in spermatogenesis, steroidogenesis and testicular architecture in SD rat: Protection from an alternative herbal viagra.

INTRODUCTION: The children and adolescents with cancer who are getting remission and becoming long-term survivals are at high risk of impaired fertility. Cyclophosphamide (CP), the most frequently used drug for childhood-cancers causes various types of reproductive toxicity. We aimed at evaluating protective role of chlorophytum borivillianum (CB) extract against pre-pubertal CP exposure-induced testicular toxicity in rats. MATERIALS AND METHODS: Sixty male pre-pubertal SD rats aged postnatal day (PND) 24 were divided into 5 groups. Group-I (control), group-II (CP), and group-III (CB) received normal saline (NS), CP15mg/kg/day and CB200mg/kg/day respectively during PND29-42; group-IV and group-V received CB100mg/kg/day and CB200mg/kg/day respectively along with CP15mg/kg/day for the same period. Half of the rats from each group were sacrificed on PND43 (puberty) to evaluate alterations in oxidative stress parameters and histopathology. Remaining rats were sacrificed on PND63 (young adult age) and sperm analysis (density, motility, viability, and morphology), hormonal (Testosterone, Luteinizing hormone, Follicle stimulating hormone) estimation and histomorphometrical evaluation was done. Co-administration of CB have shown a dose-dependent and significant improvement in anomalies caused by CP as compared to rats received CP only. RESULTS: CP treatment led to significant decrease in body weight gain, organ weights, oxidative defense mechanisms, hormone levels, steroidogenesis, spermatogenesis, sperm parameters and increase in oxidative stress, percentage of sperm abnormal morphology as compared to control rats. CP-treated rats have shown severe damage in testicular architecture and development as compared to control rats as evidenced by histopathology and morphometric analysis. CONCLUSION: Co-administration of CB extract significantly reversed the footprints of these effects in dose-dependent manner. These protective effects of CB may be exploited in improving gonadal function in childhood cancer long-term survivals.

Alpha-lipoic acid ameliorates cytarabine-induced developmental anomalies in rat fetus.

Cytarabine (Ara-C) is a nucleoside analogue used in the treatment of cancers and viral infections. It has teratogenic potential and causes a variety of birth defects in fetuses. Alpha-lipoic acid (ALA) is a natural antioxidant offers protection against the developmental toxicity induced by drug- or toxicant-exposure or pathological conditions. This study was aimed at evaluating the protective effect of ALA against Ara-C induced developmental toxicity in rat fetus. Pregnant rats divided into five groups and received normal saline, ALA200 mg/kg, Ara-C12.5 mg/kg, Ara-C25 mg/kg and, Ara-C25 mg/kg plus ALA200 mg/kg respectively from gestational day (GD) 8 to GD14 and sacrificed on GD21. Ara-C treatment led to a significant and dose-dependent decrease in food intake, weight gain, placental weight, and an increase in oxidative stress in pregnant rats. Further, the in-utero exposure to Ara-C led to an increase in fetal mortality, resorptions, oxidative stress, external morphological anomalies and limb abnormalities, and impaired ossification. Co-administration of ALA resulted in amelioration of the footprints of Ara-C induced toxicity in pregnant rats as well as the fetus. These findings indicate that the ALA supplementation offers protection against developmental toxicity caused by Ara-C prenatal exposure in rats.

A cross sectional study reveals severe disruption in glycemic control in people with diabetes during and after lockdown in India.

BACKGROUND AND AIMS: Uncontrolled diabetes has been associated with poorer clinical outcomes in COVID-19. We aimed to evaluate and assess the impact of COVID-19 pandemic on management of diabetes and challenges faced by people with diabetes in India during and after the lockdown phase. METHODS: A cross-sectional study based on an online questionnaire survey was designed. The questions collected socio-demographic details, medical and social history, and impact of the pandemic on medical and social life from 1582 participants. Linear regression was employed to evaluate association of different parameters with the change in glycemic levels. RESULTS: The frequency of clinical visits during the COVID-19 pandemic were reduced in 87.28% of participants. 92.45% of participants were able to monitor their blood glucose levels (BGLs) in which 78.42% (49.35%, 20.91%, and 8.16%) participants experienced an increase in BGL (mild, moderate, and severe respectively). Only 47.41% of participants possessed the digital glucometer at home. 69.07% of participants reported a decrease in physical activity while 46.88% reported an increase in food intake. 80.06% of participants were able to buy all medicines and 29.80% were gone for virtual consultations while 87.81% reported that they didn't have access to healthcare services. Overall, 89.47% participants experienced disruption in therapy. A highly significant correlation (r = 0.89, p = 0.0145) was found between increasing age and reporting of higher BGLs. CONCLUSION: This study provides a firsthand evidence of major disruption in diabetes care activities during and after the lockdown phase in India and increased risk of poorer clinical outcomes, if infected by SARS-CoV-2.

A Case of Acute Generalized Exanthematous Pustulosis by Cefixime with Oral Mucosal Involvement.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction characterized by the development of numerous sterile and non-follicular pustules on an erythematous base with no or minimal mucous membrane involvement associated with fever and leucocytosis. Cefixime is a cephalosporin-type beta-lactam antibiotic commonly used for the management of several infections. The Cefixime-induced AGEP cases are known to be rare. Here, we present the case report of a 26-year old female who developed Cefixime-induced AGEP with mucosal membrane involvement. To the best of our knowledge, this is the first case to report the mucosal membrane involvement in Cefixime-induced AGEP. We are presenting this case report to draw the attention on the existence and plethora of symptoms of Cefixime-induced AGEP hoping that the clinicians will reckon these in their differential diagnosis and implement the appropriate management strategies for this rare adverse event in their clinical practice.