Melatonin abrogates liver, ovarian, and uterine toxicities induced by tamoxifen in a breast cancer mouse model

Melatonin is known for its efficacy in breast cancer treatment. However, the safety profile of melatonin, particularly its effect on liver, uterus and ovaries is largely unknown. Here, we explored the safety profile of melatonin using virgin female mice of the Swiss albino strain. Further, we investigated whether melatonin can overcome liver, ovaries and uterine toxicities which are induced by tamoxifen using N,N-dimethylbenzylamine (DMBA) induced breast cancer mouse model? Treatment of tamoxifen after breast cancer induction in mice resulted in reduction of breast masses but severe pathological abnormalities like liver steatosis, hyper ovulation, ovarian cysts, uterine glands dilatations and endometriosis were observed in treated animals. Whereas, melatonin when used in combination with tamoxifen helped to reduce the mouse mammary tumor volume and significantly decreases liver enzymes, steroid hormones and oxidative stress. Melatonin also reverted the liver, ovarian and uterus toxicity induced by tamoxifen. The results have demonstrated that tamoxifen when used as combination therapy with melatonin serve as an effective anti-breast cancer molecule with minimum liver, ovarian and uterus toxicities

Melatonin abrogates liver, ovarian, and uterine toxicities induced by tamoxifen in a breast cancer mouse model

33-43Melatonin is known for its efficacy in breast cancer treatment. However, the safety profile of melatonin, particularly its effect on liver, uterus and ovaries is largely unknown. Here, we explored the safety profile of melatonin using virgin female mice of the Swiss albino strain. Further, we investigated whether melatonin can overcome liver, ovaries and uterine toxicities which are induced by tamoxifen using N,N-dimethylbenzylamine (DMBA) induced breast cancer mouse model? Treatment of tamoxifen after breast cancer induction in mice resulted in reduction of breast masses but severe pathological abnormalities like liver steatosis, hyper ovulation, ovarian cysts, uterine glands dilatations and endometriosis were observed in treated animals. Whereas, melatonin when used in combination with tamoxifen helped to reduce the mouse mammary tumor volume and significantly decreases liver enzymes, steroid hormones and oxidative stress. Melatonin also reverted the liver, ovarian and uterus toxicity induced by tamoxifen. The results have demonstrated that tamoxifen when used as combination therapy with melatonin serve as an effective anti-breast cancer molecule with minimum liver, ovarian and uterus toxicities

Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice

Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in the liver and spleen manifested by hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen is represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system. Keywords: Captopril, Mice, Liver, Splee

Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice

Background: Kidney is a vital organ which plays an important and irreplaceable role in detoxification and removal of xenobiotics. And therefore is vulnerable to develop various forms of injuries. Hence, making it immensely important to search for natural reno-protective compounds. Objectives: This study therefore, aims to evaluate the reno-protective properties of propolis against gentamicin induced renal toxicity in mice. Methods: Three groups of 10 male mice each were used for this study. First group served as control, the second group (Gm group) was administered orally 80 mg/kg body weight gentamicin for 7 days, and the third group (GmP group) was administered same dose of gentamicin with propolis (500 mg/kg body weight) for 7 days. Various parameters were used to study the renal toxicity. Results: Gentamicin caused significant renal damage as evident by the rise in BUN levels, diminished glomeruli hypocellularity, moderately dilated tubules, and mild loss of brush border, severe infiltration, extensive tubular degeneration and presence of tubular cast. Histochemistry results show presence of collagen and reticular fibres. Immunohistochemical reactions show kidney injury (Kim-1 gene-expression), oxidative stress (MDA gene-expression), and an increase in apoptosis (caspase-3 gene-expression). Co-administration of propolis with gentamicin showed significant decrease in BUN levels, appearance of healthy glomeruli with normal cellularity, reduction of tubular injury, decrease of collagen and reticular fibres deposition, reduction of apoptosis, kidney injury and oxidative stress. Conclusion: Results presented in this study clearly show the reno-protective role of propolis against gentamicin-induced toxicity on mice kidney

A novel homozygous splice site variant in the CLCN7 causes osteopetrosis

Objectives: Osteopetrosis is a monogenic disorder represented by disturbed osteoclast resorption or osteoclastogenesis differentiation. Clinical symptoms are intensive and brittle bones, recurrent fractures, thrombocytopenia, impaired immune function, optic nerve compression, and anemia. Several osteopetrosis-causing genes have been identified and reported. Methods: The present study describes two consanguineous Saudi families segregating a severe autosomal recessive osteopetrosis disease. A single proband (II-2) in family A and two probands (II-2; II-4) in family B exhibited increased bone density, multiple fractures, teeth abnormalities, bilateral optic atrophy with nystagmus, and progressive blindness. DNA of the affected individuals was exposed to whole-exome sequencing (WES) and Sanger sequencing. Further, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting analysis were done to investigate the impact of the identified mutation. Results: WES revealed a novel homozygous splice site variant (c.739-18G > A) in the CLCN7 gene on chromosome 16p13.3, segregating perfectly with the disorder phenotype. RT-PCR resulted in the retention of a 50 bp sequence of intron 8 in the mutated sequence. As a result, this variant resulted in a large size exon 9 compared to the wild type. In addition, the western blot revealed the heteromeric form of ClC-7 disappeared in the patient’s fibroblasts versus the control, indicating identified variant pathogenicity. Conclusion: The present research provides certain proof that homozygous variants in the CLCN7 gene are responsible for intense osteopetrosis disorders with diverse phenotypes. These findings have significant implications for decisions regarding the clinical therapeutic regimen, prognosis assessment, and antenatal diagnosis

ONECUT2 regulates proliferation and apoptosis in glioblastoma cell lines

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor associated with a high mortality rate, with an average survival time of less than two years. GBM treatment faces significant challenges due to its infiltrative nature, genetic diversity, protection by the blood–brain barrier (BBB), drug resistance, and post-treatment side effects. Transcription factors (TFs) play a crucial role in regulating gene expression during cancer initiation and progression. This study aimed to investigate the impact of altering the function of ONECUT-2 (OC-2) in GBM cells, focusing on metabolic activity, proliferation, cell cycle, and apoptosis. To confirm the successful reduction of OC-2 expression in U251 and U87 cells compared to the control cells (wild types; WT), quantitative real-time polymerase chain reaction (qPCR) was performed. The downregulation of OC-2 resulted in a significant decrease in metabolic activity (MTT) of U251 cells by 47 % (P = 0.0056) and U87 cells by 36.4 % (P = 0.0003) compared to WT cells. In U251 cells, OC-2 downregulation caused cell cycle arrest in both the G0/G1 phase (13.6 %) and the S/G2 phase (52.52 %) compared to WT cells. Similarly, in U87 cells, downregulation of OC-2 led to cell cycle arrest in the G0/G1 phase (90.5 %) and the G2 phase (76.61 %) compared to WT cells. Furthermore, OC-2 downregulation significantly affected early-stage apoptosis in U251 cells (95.46 %, P = 0.0005) and U87 cells (19.64 %, P = 0.0004). Conversely, upregulation of OC-2 significantly increased the metabolic activity (MTT) of U251 cells by 94 % (P = 0.0067) and U87 cells by 58 % (P = 0.0028) compared to WT cells. These findings highlight the essential role of OC-2 in regulating the progression of GBM cells. Consequently, OC-2 represents a potential therapeutic target for inhibiting GBM. Overall, this study demonstrates that OC-2 plays a significant role in cell progression, suggesting its potential as a therapeutic target for GBM treatment

Crystal Growth and Kinetic Behaviour of Pseudoalteromonas espejiana Assisted Biosynthesized Gold Nanoparticles

Pseudoalteromonas espejiana (P. espejiana) is a marine bacterium known for its high resistance to alkalinity. The ability of P. espejiana to reduce Au (III) and biosynthesize gold nanoparticles (AuNPs) is found positive and was confirmed using UV-VIS, EDS, SEM, and TEM studies. Previously, many studies have been reported regarding the crystalline nature of AuNPs; therefore, this research aims at studying the crystal growth behaviour of AuNPs through DLS and TEM studies. Spherically shaped and monodispersed, AuNPs ranging between 5 to 160 nm were obtained with an average particle size of 62 nm. Also, to achieve maximum production of AuNPs, the reaction kinetic study was performed using an ICP-OES method and the effect of various parameters including pH, temperature, rpm, and concentration of substrate was analyzed. During the biosynthesis process, an appropriate phase of nucleation, crystal growth, and saturation was observed and this helped to determine the rate constants and order of reaction. The parameters such as pH profile (pH 9), temperature (30°C), agitation speed (150 rpm), and enzyme substrate ratio (2 : 3) were found to be the best fits for maximum production of low size AuNPs. This demonstrates that in initial few hours, a quick conversion of the ionic gold precursor takes place into metallic gold nuclei, trailed by crystal growth via coalescence of small nuclei. Subsequently, it can be concluded that coalescence processes drive the crystal growth process of AuNPs over a time interval and finally leads to saturation and no newer particle formation in the solution