Trastuzumab (TZM) is a humanized monoclonal antibody that has been approved for the clinical management of HER2-positive metastatic breast and gastric cancers but its use is limited by its cumulative dose and off-target cardiotoxicity. Unfortunately, till date, there is no approved antidote to this off-target toxicity. Therefore, an acute study was designed at investigating the protective potential and mechanism(s) of CVE and IGE in TZM-induced cardiotoxicity utilizing cardiac enzyme and oxidative stress markers and histopathological endpoints. 400mg/kg/day CVE and IGE dissolved in 5 DMSO in sterile water were investigated in Wistar rats injected with 2.25mg/kg/day/i.p. route of TZM for 7 days, using serum cTnI and LDH, complete lipid profile, cardiac tissue oxidative stress markers assays, and histopathological examination of TZM-intoxicated heart tissue. Results showed that 400mg/kg/day CVE and IGE profoundly attenuated increases in the serum cTnI and LDH levels but caused no significant alterations in the serum lipids and weight gain pattern in the treated rats. CVE and IGE profoundly attenuated alterations in the cardiac tissue oxidative stress markers activities while improving TZM-associated cardiac histological lesions. These results suggest that CVE and IGE could be mediating its cardioprotection via antioxidant, free radical scavenging, and antithrombotic mechanisms, thus, highlighting the therapeutic potentials of CVE and IGE in the management of TZM-mediated cardiotoxicity.

Phytomedicines reportedly rich in cystine knot peptides (Knottins) are found in several global diets, food/herbal supplements and functional foods. However, their knottin peptide content has largely been unexplored, notably for their emerging dual potentials at both the food and medicine space. The nutritional roles, biological targets and mechanism(s) of activity of these knotted peptides are largely unknown. Meanwhile, knottins have recently been unveiled as emerging peptide therapeutics and nutraceuticals of primary choice due to their broad spectrum of bioactivity, hyper stability, selective toxicity, impressive selectivity for biomolecular targets, and their bioengineering applications. In addition to their potential dietary benefits, some knottins have displayed desirable limited toxicity to human erythrocytes. In an effort to appraise what has been accomplished, unveil knowledge gaps and explore the future prospects of knottins, an elaborate review of the nutritional and pharmaceutical application of phytomedicines rich in knottins was carried out. Herein, we provide comprehensive data on common dietary and therapeutic knottins, the majority of which are poorly investigated in many food-grade phytomedicines used in different cultures and localities. Findings from this review should stimulate scientific interest to unveil novel dietary knottins and knottin-rich nutraceutical peptide drug candidates/leads with potential for future clinical application.

Background: Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets. Method: A total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day). Results: Pro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats. Conclusion: This study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.

Background: Emerging evidence indicates that certain chemotherapeutic agents, particularly the bleomycin, etoposide, and cisplatin (BEP) regimen, exert deleterious effects on male reproductive function, including impaired spermatogenesis. Previous studies have demonstrated that Garcinia kola (GK) seed extract and its bioactive biflavonoid constituent, kolaviron (KV), exhibit beneficial properties in reproductive physiology. However, their potential protective effects against BEP‐induced testicular toxicity remain underexplored. This study evaluated the chemopreventive efficacy of GK extract (GKE) and KV in attenuating BEP‐mediated testicular damage in a preclinical rodent model. Methods: Adult male Wistar rats ( n = 8 per group) were subjected to three 21‐day cycles of BEP chemotherapy (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin, administered intraperitoneally). Concurrently, treatment groups received oral supplementation with GKE (100 mg/kg), KV (100 mg/kg), silymarin (SLM; 10 mg/kg), or prednisolone (PRED; 5 mg/kg), with dosages determined via prior dose–response optimization. Post‐treatment assessments included: sperm functional analysis (count, motility, morphology), serum reproductive hormone profiling [testosterone (TST), luteinizing hormone (LH), follicle stimulating hormone (FSH)], oxidative stress markers [glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione‐S‐transferase (GST)], lipid peroxidation indicators [malondialdehyde (MDA), nitric oxide (NO)], inflammatory cytokines (TNF‐α, IL‐6), and apoptotic markers [caspase‐3 (CAS‐3) and caspase‐9 (CAS‐9)]. Results: BEP administration significantly impaired spermatogenic output, which was ameliorated by GKE, KV, SLM, and PRED co‐treatment. Notably, TST levels remained stable in GKE‐ and KV‐supplemented groups. All test compounds enhanced antioxidant capacity, suppressing lipid peroxidation (reduced MDA and NO). Furthermore, GKE and KV significantly attenuated BEP‐induced elevations in pro‐inflammatory cytokines (TNF‐α, IL‐6) and apoptotic mediators (CAS‐3, CAS‐9). Conclusion: GKE and KV conferred substantial protection against BEP‐induced testicular toxicity, primarily through mechanisms involving oxidative stress mitigation, anti‐inflammatory action, and apoptosis suppression. Their efficacy paralleled that of established agents (SLM, PRED), suggesting potential utility as adjunctive therapies to preserve male fertility during chemotherapy. These findings warrant further clinical investigation to assess translational applicability.

Background: Kafura pelebe (camphor) {C10H16O} is a chemical substance used mostly amongst the Yoruba ethnic group in Western Nigeria to treat infantile colic during early childhood. This study assess the neurotoxic potentials of Kafura following sub-chronic exposure in female albino Wistar rats. Methods: Twenty-eight female rats (mean weight of 130 g) were randomly selected and assigned into four (4) groups. Control, received 1ml coconut oil while the treatment groups received 79, 158 and 237. mg/kg b.wt (d ose p.o) of Kafura for the period of 14 days. On day fifteen, animals were dissected and the brain organ excised for the homogenate and histopathologic assay, blood samples were also collected for haematological analysis. Morris Water Maze experiment for reference memory was also carried out to ascertain effect of Kafura in the Central Nervous system (CNS). Results: A trend toward decreased body-weight gain and increase brain weight was observed in Kafura-treated rats but was statistically not significant, compared to control. The biochemical assessment of the antioxidant status of brains of Kafura-treated rats showed significant (p <= 0.05) increase in activities of some anti-oxidant enzymes (Superoxide dismutase (SOD), Glutathione peroxide (GPx), and Catalase (CAT)). There was increase in acetylcholinesterase (AChE), Malondialdehyde (MDA), and Total protein activities in the brain of treated rats compared to control. Alterations of the haematological parameters were observed, with the plasma granulocytes, lymphocytes, and haemoglobin (HGB), showing significant decrease in the treated rats compared to control. The water maze test showed a marked increase in spatial learning and memory time (seconds) in kafura-treated rats, compared to control and across treated groups. Conclusions: The present study provides indication that kafura Pelebe shows apparent neurotoxicity in experimental animals. Incessant exposure in humans though may lead to development of some central nervous system defects.

Background and Purpose: A Nigerian-formulated polyherbal supplement (PHS) is consumed for its folkloric claims of boosting the immune system. The aim of this study was to toxicologically evaluate a 30-day administration of PHS. Methods: Gas Chromatography/Mass Spectrometry (GC/MS) analysis was carried out on the ethanol extract of PHS. Thirty-two Wistar rats were randomly assigned to four groups. One group served as control while the other three groups were administered 250, 500, and 1000 mg/kg/day of PHS for 30 consecutive days. The animals were anesthetized, and cardiac puncture was used to obtain whole blood for hematology and serum biochemistry. In vivo, antioxidant assays were also carried out on the liver homogenates. The liver, kidneys, and heart were examined histologically. Results: The most abundant compounds identified were eucalyptol, alpha-pinene, and phytol. There were no adverse hematological effects. Total cholesterol, LDL-C, and catalase were reduced significantly (P<0.05). At 1000 mg/kg/day, there was a significant increase in creatinine, sodium ion, and glutathione peroxidase concentration. The histological examination of the heart, kidneys, and liver revealed that PHS did not cause any major tissue lesions at 250 and 500 mg/kg/day. Tissue lesions and pathologies were obvious at 1000 mg/kg/day. Conclusion: The polyherbal supplement seems to be relatively safe if used at doses up to 250 mg/kg/day. Higher doses may cause renal and hepatic lesions.