The Impact of Metformin on the Development of Hypothyroidism and Cardiotoxicity Induced by Cyclophosphamide, Methotrexate, and Fluorouracil in Rats

Cyclophosphamide (CYP), methotrexate (MTX), and 5-fluorouracil (5-FU) are extensively utilized in the therapeutic management of various malignancies. It is noteworthy, however, that potential chemotherapy-related complications include the occurrence of hypothyroidism and cardiotoxicity. Metformin (MET) is a pharmacological agent for managing type 2 diabetes. It has been reported to mitigate certain toxic manifestations associated with chemotherapy. This study’s primary objective is to investigate MET’s protective effects against hypothyroidism and cardiotoxicity induced by CMF treatment. A total of forty male rats were allocated into four distinct groups, each consisting of ten rats per group. These groups were categorized as follows: saline, MET, CMF, and CMF + MET. The experimental group of rats were administered CMF via intraperitoneal injection, receiving two doses of CMF, and fed MET in their daily drinking water, with a 2.5 mg/mL concentration. Blood samples were collected into EDTA tubes for assessment of TSH, free and total (T4 and T3), troponin I, CK, and CK-MB levels utilizing Electrochemiluminescence Immunoassays (ECI). The saline and MET groups did not exhibit significant alterations in thyroid hormones or cardiotoxic biomarkers. In contrast, in the CMF group, there was a notable reduction in T4, FT4, T3, and FT3 levels but no significant changes in TSH levels; however, troponin I, CK, and CK-MB levels were notably elevated. MET co-treatment with CMF did not ameliorate these effects caused by CMF. In conclusion, CMF treatment induced hypothyroidism and cardiotoxicity in rats, but MET co-treatment did not rescue the reduction of thyroid hormones or the elevation of cardiotoxic biomarkers

The Ameliorative Effect of Pioglitazone against Neuroinflammation Caused by Doxorubicin in Rats

Doxorubicin (DOX) is a chemotherapeutic agent that is linked with complications such as cardiotoxicity and cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are no known therapeutic options for its treatment. This study aimed to determine the protective effect of pioglitazone (PIO) against DOX-induced cognitive impairment. Forty Wistar female rats were equally divided into four groups: control, DOX-treated, PIO-treated, and DOX + PIO-treated. DOX was administered at a dose of 5 mg/kg, i.p., twice a week for two weeks (cumulative dose, 20 mg/kg). PIO was dissolved in drinking water at a concentration of 2 mg/kg in the PIO and DOX-PIO groups. The survival rates, change in body weight, and behavioral assessment were performed using Y-maze, novel object recognition (NOR), and elevated plus maze (EPM), followed by estimation of neuroinflammatory cytokines IL-6, IL-1β, and TNF-α in brain homogenate and RT-PCR of a brain sample. Our results showed a survival rate of 40% and 65% in the DOX and DOX + PIO groups, respectively, compared with a 100% survival rate in the control and PIO treatment groups at the end of day 14. There was an insignificant increase in body weight in the PIO group and a significant reduction in the DOX and DOX + PIO groups as compared with the control groups. DOX-treated animals exhibited impairment of cognitive function, and the combination PIO showed reversal of DOX-induced cognitive impairment. This was evidenced by changes in IL-1β, TNF-α, and IL-6 levels and also by mRNA expression of TNF- α, and IL-6. In conclusion, PIO treatment produced a reversal of DOX-induced memory impairment by alleviating neuronal inflammation by modulating the expression of inflammatory cytokines

Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats

Methotrexate (MTX; 4-amino-10-methylfolic acid) is a folic acid reductase inhibitor used to treat autoimmune diseases and certain types of cancer. Testicular toxicity resulting from MTX is a significant side effect that may cause subsequent infertility. The present study was conducted to examine the ameliorating effects of vitamin B17 (VitB17) against testicular toxicity induced by MTX in male rats. A total of 50 male albino rats were equally divided into five groups [control group; vitamin B17 group (VitB17) administered VitB17 only; methotrexate group administered MTX only; cotreated group, (VitB17+MTX) and posttreated group (MTX+VitB17)]. In methotrexate group (MTX), a significant decrease was observed in body weight and the testicular weight, as well as the levels of plasma testosterone, luteinizing hormone and follicle-stimulating hormone compared with control. The sperm count, viability, morphology index, total motility, and progressive motility also decreased in MTX rats compared with control. Furthermore, the levels of reduced glutathione, catalase, and superoxide dismutase, as well as proliferating cell nuclear antigen protein expression, in the testicular tissue decreased in MTX compared with control. In addition, MTX caused a significant increase in DNA and tissue damage compared with control. However, VitB17 ameliorated these effects, indicating that it has a preventative and curative effect against MTX-induced reproductive toxicity in male rats. The protective effect of VitB17 may be associated to its antioxidant properties as it possibly acts as a free-radical scavenger and lipid peroxidation inhibitor, as well as its protective effect on the levels of GSH, SOD, and CAT

The impact of chicory (Cichoriumintybus L.) on hemodynamic functions and oxidative stress in cardiac toxicity induced by lead oxide nanoparticles in male rats

Background: A common environmental pollutant, lead can induce toxicity in several organ systems. A range of industrial and/or household materials and products contain lead, and food/liquid ingestion and inhalation are the mechanisms through which lead is introduced into the human body. Objective: Since knowledge about the cardiac toxicity of acute lead nanoparticles is limited, this work sought to shed more light on the issue by investigating the therapeutic effects of chicory extract based on rat models to elevate cardiac functions and oxidative stress. Methods: Four research groups were used, each consisting of ten albino rats of male sex and adult age. The groups were: control group, chicory group, lead oxide nanoparticle group, and lead oxide nanoparticle + chicory group. Results: Compared to the control and chicory groups, the lead oxide nanoparticle group displayed a notable increase in heart functions and oxidative stress markers as well as alterations in cardiac histological structure. On the other hand, cardiac function modifications were counteracted through four-week administration of lead oxide nanoparticles alongside chicory. Conclusion: Heart damage caused by lead oxide nanoparticles may be attenuated by chicory through scavenging of free radicals

Comparative evaluation of doxorubicin, cyclophosphamide, 5-fluorouracil, and cisplatin on cognitive dysfunction in rats: Delineating the role of inflammation of hippocampal neurons and hypothyroidism

Chemotherapeutic agents such as doxorubicin, cyclophosphamide, fluorouracil, and cisplatin are commonly used to treat a variety of cancers and often result in chemobrain, which manifests as difficulties in learning and memory processes that can persist in the years following treatment. The current study aims to evaluate the cognitive function following treatment with these agents and the underlying mechanisms using a rat model of neuroinflammation and possible implication of thyroid toxicity in chemotherapy induced cognitive dysfunction. Wistar female rats were treated with a single dose of doxorubicin (DOX, 25 mg/kg), 5-fluorouracil (5-FU, 100 mg/kg), cisplatin (8 mg/kg), and cyclophosphamide (CYP, 200 mg/kg) by intraperitoneal injection. The cognitive performance of rats was then evaluated in spatial memory tasks using the Y-maze, novel object recognition (NOR), and elevated plus maze (EPM) tests. Serum levels of thyroid hormones (T3, T4, FT3, and FT4) and thyroid stimulating hormone (TSH) were measured, followed by estimation of TNFα, IL-6, and IL-1β in the hippocampal tissue. Results revealed that all the chemotherapeutic agents produced impairment of cognitive function, and significant increase of pro-inflammatory cytokines such as TNFα, IL-6 and IL-1β in the hippocampal tissues. There was a significant reduction in thyroid hormones (T3, FT3, and T4) and an increase in thyroid stimulating hormone (TSH) in serum, which may also have contributed to the decline in cognitive function. In conclusion, DOX, 5-FU, CYP, and cisplatin produces impairment of spatial memory possibly by inflammation of hippocampal neurons and endocrine disruption (hypothyroidism) in rats

Formulation of Ethyl Cellulose Microparticles Incorporated Pheophytin A Isolated from <i>Suaeda vermiculata</i> for Antioxidant and Cytotoxic Activities

Background: This study is designed to discover a method for delivering an efficient potent pheophytin a (pheo-a) into more absorbed and small polymeric ethyl cellulose (EC) microparticles. Methods: Silica gel and Sephadex LH-20 columns were used to isolate pheo-a from the chloroform extract of the edible plant, Suaeda vermiculata. Pheo-a was incorporated into EC microparticles using emulsion-solvent techniques. The antioxidant activity of pheo-a microparticles was confirmed by the level of superoxide radical (SOD), nitric oxide (NO), and reducing power (RP) methods. Meanwhile, the cytotoxic effect of the product was investigated on MCF-7 cells using MTT assay. Results: Pheo-a was isolated from S. vermiculata in a 12% concentration of the total chloroform extract. The structures were confirmed by NMR and IR spectroscopic analysis. The formulated microparticles were uniform, completely dispersed in the aqueous media, compatible as ingredients, and had a mean diameter of 139 &#177; 1.56 &#181;m as measured by a particle size analyzer. Pheo-a demonstrated a valuable antioxidant activity when compared with ascorbic acid. The IC50 values of pheo-a microparticles were 200.5 and 137.7 &#181;g/mL for SOD, and NO respectively. The reducing power of pheo-a microparticles was more potent than ascorbic acid and had a 4.2 &#181;g/mL for IC50 value. Pheo-a microparticles did not show notable cytotoxicity on the MCF-7 cell line (IC50 = 35.9 &#181;g/mL) compared with doxorubicin (IC50 = 3.2 &#181;g/mL). Conclusions: the results showed that water-soluble pheo-a microparticles were prepared with a valuable antioxidant activity in a wide range of concentrations with a noteworthy cytotoxic effect

Silver citrate nanoparticles inhibit PMA-induced TNF alpha expression via deactivation of NF-kappa B activity in human cancer cell-lines, MCF-7

Background: The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer’s onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. Objective: The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. Methods: The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11– 7082. Results: The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381– 452 nm wherein the particles size ranged between 19.2± 0.1 to 220.77± 0.12 nm with the charge range − 9.99± 0.8 to − 34.63± 0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at > 40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. Conclusion: This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders

Body mass index, vital signs, Liver function tests, blood glucose level, kidney function tests and oxidative stress biomarkers for the control and the cannabis user group s [n = 120] before and after treatment.

Body mass index, vital signs, Liver function tests, blood glucose level, kidney function tests and oxidative stress biomarkers for the control and the cannabis user group s [n = 120] before and after treatment.</p

Schematic diagram of the study design.

The abuse of Cannabis is a widespread issue in the Asir region. It has a lot of legal and occupational repercussions. The purpose of this study was to evaluate the health status of cannabis addicts at admission and after treatment using body mass index, glycemic status, liver function, renal function, and oxidative stress. A cross-sectional study was conducted with 120 participants. The study was conducted at Al Amal Hospital for Mental Health in Asir region of Saudi Arabia, with 100 hospitalized patients receiving addiction treatment and 20 healthy volunteers. The participants were divided into two groups: group I, the control group, and group II, the cannabis addicts. The socio-demographic data were gathered. The level of cannabis in the urine and the CWAS [Cannabis Withdrawal Assessment Scale] were determined. In addition, the Body Mass Index [BMI], vital signs [temperature, heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate], serum levels of albumin, total bilirubin, direct bilirubin, AST, ALT, and ALP, urea, creatinine, Thiobarbituric acid-reactive substances [TBARS], superoxide dismutase [SOD], reduced glutathione [GSH], and catalase [CAT] were analyzed on the first day of admission and after treatment. According to the results, there was no significant change in the body mass index. The vital signs in the cannabis user group were significantly lower than the corresponding admission values. Regarding renal function tests such as urea and creatinine, we found that after treatment, the mean urea and creatinine values in the cannabis user group did not differ significantly from the corresponding admission values. However, after treatment, the mean values of fasting blood glucose levels in the cannabis user group were significantly lower than at admission. Also, the mean values of liver function tests such as albumin, total bilirubin, direct bilirubin, AST, ALT, and ALP in the cannabis user group were significantly lower than the corresponding admission values after treatment. In assessing the antioxidant system, we found that the mean values of TBARS, SOD, GSH, and CAT in the cannabis user group did not differ significantly from the corresponding admission values after treatment. The current findings have revealed that cannabis addiction harms the various body systems and has significant implications for the addict’s state of health. The values of oxidative stress biomarkers did not change in this study, but other measured parameters improved after treatment.</div