Interest is growing in finding natural sources of effective antitumor agents that generate fewer side effects than conventional chemotherapeutic drugs. Avenanthramides (Avns) are such compounds; these phenolic molecules naturally occur in oats and have antioxidant, anti-inflammatory, and antiproliferative effects making them worthy of further research. The aim of this study is to characterise Avns’ curative ability and antineoplastic activity on solid-form Ehrlich tumors. For the study, 75 female mice were randomly and equally allocated to five groups (group 1-control, group 2-DMSO, group 3-positive control receiving Avns, group 4-mice with Ehrlich solid tumor, and group 5-Ehrlich solid tumor treated with Avns). Mice with Ehrlich solid tumors exhibit increased tumor volume; elevated expression of AFP, ALT, AST, Bcl2, CEA, cholesterol, creatinine, urea, MDA, PCNA, potassium, triglycerides, TNF-α, and NF-κB; and a concomitant decline in catalase, GSH, P53, and SOD. In the mice with Ehrlich tumors who received Avns, there appeared to be improvement in NF-κB TNF-α, tumor markers (AFP and CEA), electrolytes, liver and kidney function enzymes, and lipid profiles; reduced MDA level; improved antioxidant parameters; normalised liver protein, P53, and PCNA; and reduced Bcl2 expression. Pathological examination of tumor lesions also indicated improvement. These results suggest that Avns exhibit antineoplastic activity and possess antioxidant properties that enhance the antioxidant defence system, thus reducing the oxidative stress caused by Ehrlich solid tumors.

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.

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 ± 1.56 µm 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 µg/mL for SOD, and NO respectively. The reducing power of pheo-a microparticles was more potent than ascorbic acid and had a 4.2 µg/mL for IC₅₀ value. Pheo-a microparticles did not show notable cytotoxicity on the MCF-7 cell line (IC₅₀ = 35.9 µg/mL) compared with doxorubicin (IC₅₀ = 3.2 µg/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.

Background and aims: Doxorubicin (DOX) causes cognitive impairment (chemobrain) in patients with cancer. While DOX damages the cholinergic system, few studies have focused on the protective effects of cholinergic function on chemobrain. The acetylcholinesterase inhibitor galantamine (GAL) demonstrates neuroprotective properties. We investigated the mechanisms associated with DOX-induced cognitive impairments and the potential protective role of GAL in preventing chemobrain. Main methods: Female Wistar rats were divided into control, DOX, GAL, and DOX + GAL groups. The rats in the DOX group were administered DOX (5 mg/kg intraperitoneally twice weekly for two weeks), while those in the GAL group were orally administered GAL (2.5 mg/kg) via oral gavage once daily for 15 days. The combination group (DOX + GAL) received GAL (once daily) and DOX (two times per week) concurrently. The body weights and survival rates were monitored daily. The animals were subjected to behavioral tests to assess the memory function followed by the biochemical estimation of inflammatory markers, including tumor necrosis factor-α (TNF-α), interleukine-1β (IL-1β), and interleukine-6 (IL-6) in rat brain tissue and RT-qPCR. Key findings: DOX caused a reduction in the body weight and survival rate, which was alleviated by GAL concomitant treatment with DOX (DOX + GAL). These groups had reduced body weights and survival rates. DOX-treated animals exhibited an impairment of short-term spatial working memory, manifested as a behavioral alteration in the Y-maze test, the novel object recognition (NOR) test, and the elevated plus-maze (EPM) test. Concurrent treatment with GAL (DOX + GAL) showed improved memory function, as evidenced by an increase in the number of entries and time spent in the novel arm, the time spent exploring the novel object, and the transfer latency in the Y-maze, NOR test, and EPM test, respectively. These findings were also supported by biochemical observations showing the reversal of DOX-induced changes in IL-1β, IL-6, and TNF-α, as well as their relative expression of mRNA in brain tissue following concurrent GAL treatment. Conclusion: GAL appeared to be a neuroprotective agent against neuroinflammation caused by DOX by reducing inflammatory markers in the brain.

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.