Cyclosporine A’s (CsA) immunosuppressive effect makes it an ideal drug for organ transplantation. However, CsA’s uses are restricted due to its side effects. We investigated the effects of avocado seed (AvS) powder on CsA-induced nephrotoxicity and immunosuppression in rats. The injection of CsA (5 mg/kg, subcutaneously, for 10 days) increased serum levels of creatinine, uric acid, and urea, and the renal levels of the malondialdehyde. It decreased creatinine clearance and the renal activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and Na⁺/K⁺ ATPase. The administration of CsA also significantly downregulated the renal expression of interferon-gamma, tumor necrosis factor-alpha, interleukin 1 beta, monocyte chemotactic protein 1, intercellular adhesion molecule-1, and vascular cell adhesion molecule 1 genes, and increased renal DNA damage. Histopathological examination confirmed the biochemical and molecular alterations that accompanied CsA nephrotoxicity. All CsA-induced deleterious effects, except immunosuppression, were ameliorated by feeding rats on a basal diet supplemented with 5% AvS powder for 4 weeks. Importantly, AvS also maximized CsA’s immunosuppressive effect. These findings suggest a potential ameliorative effect of AvS on CsA-induced nephrotoxicity, and AvS enhances CsA’s immunosuppressive effect. Therefore, AvS might be used in combination with CsA in transplantation treatment to relieve the CsA-induced nephrotoxicity.

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.

Jambolan fruit extract and choline were investigated for Aluminum tri chloride (AlCl₃)-induced Alzheimer’s disease in rats. Thirty-six male “Sprague Dawley” rats weighing (150 ± 10 g) were allocated into six groups; the first group was fed a baseline diet and served as a negative control. Alzheimer’s disease (AD) was induced in Group 2 rats by oral administration of AlCl₃ (17 mg/kg body weight) dissolved in distilled water (served as a positive control). Rats in Group 3 were orally supplemented concomitantly with both 500 mg/kg BW of an ethanolic extract of jambolan fruit once daily for 28 days and AlCl₃ (17 mg/kg body weight). Group 4: Rivastigmine (RIVA) aqueous infusion (0.3 mg/kg BW/day) was given orally to rats as a reference drug concomitantly with oral supplementation of AlCl₃ (17 mg/kg body weight) for 28 days. Group 5 rats were orally treated with choline (1.1 g/kg) concomitantly with oral supplementation of AlCl₃ (17 mg/kg body weight). Group 6 was given 500 mg/kg of jambolan fruit ethanolic extract and 1.1 g/kg of choline orally to test for additive effects concurrently with oral supplementation of AlCl₃ (17 mg/kg bw) for 28 days. Body weight gain, feed intake, feed efficiency ratio, and relative brain, liver, kidney, and spleen weight were calculated after the trial. Brain tissue assessment was analyzed for antioxidant/oxidant markers, biochemical analysis in blood serum, a phenolic compound in Jambolan fruits extracted by high-performance liquid chromatography (HPLC), and histopathology of the brain. The results showed that Jambolan fruit extract and choline chloride improved brain functions, histopathology, and antioxidant enzyme activity compared with the positive group. In conclusion, administering jambolan fruit extract and choline can lower the toxic impacts of aluminum chloride on the brain.

Heavy metal contaminated water is a great concern because of its high toxiciy, non-biodegradability, and bioaccumulation. Therefore, non-contaminated water is fundamental for a healthy life. Special attention is paid to the health-promoting ingredients of germinated whole cereal products. This study aimed to (1) examine the potentially harmful effects of Cu, Mn, and Zn on rat livers and brains, and (2) the potentially protective action of wheat and barley grasses against the expected harmful effects of these metals. The rats were treated with water contaminated by heavy metals (HMs) and germinated wheat and barley for 60 days. The rat liver functions and histopathological examinations were analyzed. Comet assay was evaluated to assess the damage in the DNA of rat livers and brains. The results indicated a significant alteration in liver functions in rats exposed to HMs; however, wheat and barley grasses at high doses decreased the harmful effects. An insignificant difference was noticed in total protein, albumin, and globulin of rats treated with HMs compared with the control. A significant increase in the serum and liver levels of HMs was recorded; however, they were reduced by wheat and barley grasses. Rat livers treated with HMs exhibited severe histological effects. The groups treated with wheat and barley grasses showed a normal liver architecture. A significant increase in DNA damage in the livers and brains was observed in rats treated with HMs, which was reduced when treated with wheat and barley grasses. Thus, using germinated seeds is promising to avoid damaging of HMs.

Long-term use of the nitroimidazole-derived antibiotic metronidazole has been associated with neuronal damage due to its ability to cross the blood–brain barrier. Polyphenol-rich plants, such as anise seeds and clove buds, are suggested to have neuroprotective effects. However, their intracellular protective pathway against metronidazole-induced neurotoxicity remains unexplored. This study aims to evaluate the potential neuroprotective benefits of anise seeds and clove buds and elucidate the proposed metronidazole-induced neurotoxicity mechanism. This study divided rats into six groups, each containing six rats. In Group I, the control group, rats were administered saline orally. Group II rats received 200 mg/kg of metronidazole orally. Group III rats received 250 mg/kg b.w. of anise seed extract and metronidazole. Group IV rats received 500 mg/kg b.w. of anise seed extract (administered orally) and metronidazole. Group V rats received 250 mg/kg b.w. of clove bud extract (administered orally) and metronidazole. Group VI rats were administered 500 mg/kg b.w. of clove bud extract and metronidazole daily for 30 consecutive days. The study evaluated the phenolic compounds of anise seeds and clove buds. Moreover, it assessed the inflammatory and antioxidant indicators and neurotransmitter activity in brain tissues. A histological examination of the brain tissues was conducted to identify neuronal degeneration, brain antioxidants, and apoptotic mRNA expression. The study found that metronidazole treatment significantly altered antioxidant levels, inflammatory mediators, and structural changes in brain tissue. Metronidazole also induced apoptosis in brain tissue and escalated the levels of inflammatory cytokines. Oral administration of metronidazole resulted in a decrease in GABA, dopamine, and serotonin and an increase in ACHE in brain tissue. Conversely, oral administration of anise and clove extracts mitigated the harmful effects of metronidazole. The neurotoxic effects of metronidazole appear to stem from its ability to reduce antioxidants in brain tissue and increase nitric oxide production and apoptosis. The study concludes that neuronal damage caused by metronidazole is significantly mitigated by treatment with anise and clove extracts.

Ethnopharmacological Relevance: Bisphenol A (BPA) is a widely used chemical, particularly in producing epoxy resins and polycarbonate plastics, which can contaminate food and water sources. Even low levels of BPA exposure have been associated with negative impacts on neural development, leading to neurotoxicity. Purple carrots, known for their health‐promoting properties, are rich in bioactive compounds such as polyphenols. Materials and Methods: This study aimed to evaluate the neuroprotective effects of purple carrot extract in mitigating BPA‐induced neurotoxicity in albino rats. Forty albino rats were divided into four groups: Group I (control) received water and a standard diet. Group II (BPA group) was orally administered 50 mg/kg body weight of BPA dissolved in 1 mL of olive oil daily for 30 days. Group III received 400 mg/kg of purple carrot extract along with 50 mg/kg of BPA daily. Group IV received 800 mg/kg of purple carrot extract along with 50 mg/kg of BPA daily, following the same 30‐day oral administration protocol. Results: The results showed that treatment with purple carrot extract increased serum levels of critical neurotransmitters, including serotonin, dopamine, acetylcholine, acetylcholineesterase, and gamma‐aminobutyric acid (GABA). Additionally, brain tissue analysis revealed elevated activity of antioxidant enzymes, such as catalase (CAT) and superoxide dismutase (SOD), in response to extract administration. Conversely, the extract significantly reduced levels of malondialdehyde (MDA), α‐tumor necrosis factor (α‐TNF), and interleukin‐6 (IL‐6) in brain tissues compared to the BPA‐only group. These results indicate that purple carrot extract regulates genes related to oxidative stress, inflammation, and apoptosis in a dose‐dependent manner during BPA‐induced neurotoxicity. At a dose of 400 mg/kg, the extract increased the expression of antioxidant genes like Nrf2 and HO‐1 while reducing the pro‐apoptotic marker Bax. At the higher dose of 800 mg/kg, these protective effects were even more pronounced, leading to enhanced neuroprotection through increased antioxidant and antiapoptotic gene expression and reduced inflammation, mainly through the MAPK pathway. Conclusion: The study demonstrates that purple carrot extract reduces BPA‐induced neurotoxicity in rats by enhancing antioxidants, neurotransmitters, and anti‐inflammatory responses, suggesting natural protection against BPA‐related neural damage.