Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis.

Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1ß), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), Caspase-3, 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1ß, iNOS, TNF-α, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67-fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity.

Anticancer activity of sinapic acid by inducing apoptosis in HT-29 human colon cancer cell line.

Colorectal cancer is the third most lethal and fourth most commonly diagnosed cancer worldwide. Sinapic acid, a derivative of hydroxycinnamic acid, is a promising phytochemical exhibiting numerous pharmacological activities in various systems. It is a substantial chain-breaking antioxidant that operates as a radical scavenger. The aim of this research was to investigate the antiproliferative effect of sinapic acid on the HT-29 cell line besides the mechanisms underlying this activity. The effect of sinapic acid on the viability of HT-29 cell line was investigated using XTT assay. The levels of BCL-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG were measured using ELISA. Gamma-H2AX and cytochrome c expressions were assessed semiquantitatively using immunofluorescence staining. Sinapic acid at 200 µm and higher doses produced a significant antiproliferative effect on HT-29 cells. The IC50 value was found to be 317.5 µm for 24 h. Sinapic acid (317.5 µm) significantly elevated cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG levels. The levels of gamma-H2AX foci are significantly higher, while the levels of cytochrome c are lower in sinapic acid-treated HT-29 cells. These results indicate that sinapic acid has antiproliferative, apoptotic, and genotoxic effects on colon cancer cells.

The Effects of Sunitinib in Healthy and Cisplatin-Induced Rats.

Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups - (1) control group (C) administered interperitoneally with a single dose 0.9 % saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1ß and TGF-ß3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.

Syringic acid guards against indomethacin-induced gastric ulcer by alleviating inflammation, oxidative stress and apoptosis.

The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-ß (TGF-ß), expressions of COX and prostaglandin E2, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.

Protective effect of Allium scorodoprasum L. ethanolic extract in cyclophosphamide-induced hepatotoxicity model in rats.

OBJECTIVES: Cyclophosphamide is a chemotherapeutic agent and immunosuppressant drug; however, it damages the liver. This study investigates the protective effect of ethanolic extract of Allium scorodoprasum (ASE) on cyclophosphamide-induced liver injury. METHODS: Twenty-eight Wistar albino rats were randomly divided into four groups (n = 7 per group): healthy rats, cyclophosphamide (200 mg/kg), cyclophosphamide (200 mg/kg) + ASE (100 mg/kg) and cyclophosphamide (200 mg/kg) + ASE (200 mg/kg). ASE was administered for 14 days, and the rats were euthanized 24 h after cyclophosphamide administration. KEY FINDINGS: Cyclophosphamide treatment leads to an increase in serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein, as well as an increase in the liver levels of malondialdehyde, tumour necrosis factor, interleukin (IL)-1ß and IL-6, while high-density lipoprotein levels decrease. Treatment with cyclophosphamide caused liver necrosis and postnecrotic cell infiltration; however, pathological changes were prevented by ASE. 8-Hydroxy-2'-deoxyguanosine, anti-4-hydroxynenal antibody and anti-dityrosine levels increased in rats treated with cyclophosphamide and decreased in the groups treated with ASE. These changes were dose dependent in the ASE-treated groups. CONCLUSIONS: Treatment with cyclophosphamide caused liver damage due to oxidative stress and inflammation. ASE regulated the damage at high doses because it has potent antioxidant and anti-inflammatory ingredients. In future studies, it may be beneficial to administer ASE in higher doses or for longer periods of time.

Mechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma.

Gambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. The cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability. ELISA was used to measure bax, BCL-2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immunofluorescence staining was applied to assess 8-oxo-dG and LC3ß levels in SNU-16 cells. It was observed that gambogic acid exerted a dose-dependent and statistically significant antiproliferative effect on SNU-16 cells. The IC50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 h. Subsequent investigations conducted using the IC50 dose revealed a significant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3ß levels (p < 0.05), a marker associated with autophagy. The antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.

The effects of sorafenib in healthy and cisplatin-treated rats.

BACKGROUND: Sorafenib is a multikinase inhibitor currently used in the treatment of hepatocellular carcinoma, renal cell carcinoma and thyroid cancer. OBJECTIVES: The literature on this agent is scarce. This study aimed to evaluate the effects of sorafenib when administered to both healthy and cisplatin-induced rats. MATERIAL AND METHODS: The animals were divided into 4 groups: 1) control group that received 0.9% saline intraperitoneally (C); 2) group administered a single dose (7 mg/kg) of cisplatin (Cis); 3) a group administered 20 mg/kg of sorafenib for 7 days (Sor); 4) group administered 20 mg/kg of sorafenib followed by 7 mg/kg of cisplatin for 7 days (Cis+Sor). All animals were sacrificed 7 days after the completion of their treatment arm, and serum and tissue samples were taken. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin 38 (IL-38) levels were increased in the Sor and Cis+Sor groups compared to the control group. When compared with the control group, serum urea, creatinine, kidney IL-1ß, and tumor necrosis factor alpha (TNF-α) levels did not change in the Sor group. When compared to the Cis group, the levels of these parameters decreased in the Cis+Sor group. CONCLUSIONS: According to the data obtained, sorafenib caused liver toxicity when given to both healthy and cisplatin-induced rats. While sorafenib did not cause any significant changes in the kidneys when given to healthy rats, it had a healing effect in kidneys after stress induced by cisplatin.

FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial pathology marked by amyloid beta (Aß) accumulation, tau hyperphosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aß levels and histological signs of neurotoxicity were detected using the enzyme-linked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aß accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD.

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats.

BACKGROUND: Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats. METHODS: The animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion+uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion+uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes. RESULTS: In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups. CONCLUSION: Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.

Aflatoxin B1 induced renal and cardiac damage in rats: Protective effect of lycopene.

This study was conducted to investigate the protective effects of lycopene against the toxic effects of Aflatoxin B1 (AFB1) exposure in kidney and heart of rat by evaluating antioxidant defense systems and lipid peroxidation (LPO). Forty-two healthy three-month-old male Wistar-Albino rats were used in this study. The animals were randomly divided into six experimental groups including 7 rats in each. These groups were arranged as follows: control group, lycopene (5 mg/kg/day, orally for 15 days) group, AFB1 (0.5 mg/kg/day, orally for 7 days) group, AFB1 (1.5 mg/kg/day, orally for 3 days) group, AFB1 (0.5 mg/kg/day, orally for 7 days) + lycopene (5 mg/kg/day, orally for 15 days) group and AFB1 (1.5 mg/kg/day, orally for 3 days) + lycopene (5 mg/kg/day, orally for 15 days) group. The animals were sacrificed at the end of applications. In this study, malondialdehyde (MDA) levels significantly increased; while reduced glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glucose-6-phosphate-dehydrogenase (G6PD) activities decreased in kidney and heart tissues. The significant reduction in the activities of antioxidant enzymes and non-enzymatic antioxidant system in AF treated rats as compared to the control group could be responsible for increased MDA levels observed during AF induced kidney and heart damage. The results showed increased urea, creatinine levels, as well as reduction sodium concentrations in plasma of AFB1 treated rats. There was lycopene showed protection against AF induced nephrotoxicity and cardiotoxicity.