Carvacrol protects rats against bleomycin-induced lung oxidative stress, inflammation, and fibrosis.

The main objective of this study was to investigate the potential efficacy of carvacrol (CAR) in mitigating bleomycin (BLM)-induced pulmonary fibrosis (PF). Sixty-six male Wistar rats were assigned into two main groups of 7 and 21 days. They were divided into the subgroups of control, BLM, CAR 80 (only for the 21-day group), and CAR treatment groups. The CAR treatment groups received CAR (20, 40, and 80 mg/kg, orally) for 7 or 21 days after an instillation of BLM (5 mg/kg, intratracheally). Results indicated that BLM significantly increased total cell count in bronchoalveolar lavage fluid and the percentages of neutrophils and lymphocytes, and reduced the percentage of macrophages. CAR dose-dependently decreased total cell count and the percentage of neutrophils and lymphocytes. CAR significantly reduced thiobarbituric acid reactive substances and hydroxyproline levels and elevated the total thiol level and catalase, superoxide dismutase, and glutathione peroxidase activities in BLM-exposed rats. Furthermore, CAR decreased the transforming growth factor-ß1, connective transforming growth factor, and tumor necrosis factor-α on days 7 and 21. BLM increased interferon-γ on day 7 but decreased its level on day 21. However, CAR reversed interferon-γ levels on days 7 and 21. Based on histopathological findings, BLM induced inflammation on days 7 and 21, but for induction of fibrosis, 21-day study showed more fibrotic injuries than the 7-day group. CAR showed the improvement of fibrotic injuries. The effect of CAR against BLM-induced pulmonary fibrosis is possibly due to its antioxidant, anti-inflammatory, and antifibrotic activity.

Betaine ameliorates arsenic-induced kidney injury in mice by mitigating oxidative stress-mediated inflammation.

Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has many beneficial health effects. This research was conducted to examine the impact of betaine on nephrotoxicity caused by inorganic arsenic (NaAsO2) in mice. Mice were separated into following groups: control, NaAsO2 (50 ppm), NaAsO2 (50 ppm) + betaine (500 mg/kg), and betaine (500 mg/kg). Mice were received NaAsO2 via drinking water for 8 consecutive weeks and betaine was given to the animals via gavage once daily in the 7th and 8th weeks of the study. Upon completion of the study, the mice were euthanized and samples of serum and kidney were obtained for further evaluations. Administration of NaAsO2 increased the levels of blood urea nitrogen and creatinine in the serum. It enhanced the amounts of renal malondialdehyde and decreased the total thiol levels, as well as the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Furthermore, it enhanced the levels of renal inflammatory indicators (tumor necrosis factor-alpha and nitric oxide). Western blot results exhibited an increase in the protein expression of nuclear factor kappa B (NF-κB), and phosphorylated NF-κB in NaAsO2-treated mice. Histopathological results also confirmed kidney damage caused by NaAsO2. However, treatment with betaine improved NaAsO2-related kidney injuries in mice. The results of this work indicated that betaine can attenuate kidney damage caused by NaAsO2 by inhibiting oxidative stress and inflammation.

Ketotifen counteracts cisplatin-induced acute kidney injury in mice via targeting NF-κB/NLRP3/Caspase-1 and Bax/Bcl2/Caspase-3 signaling pathways.

Cisplatin (CIS) stands as one of the most effective chemotherapy drugs currently available. Despite its anticancer properties, the clinical application of CIS is restricted due to nephrotoxicity. Our research aimed to specify the impact of ketotifen fumarate (KET) against nephrotoxicity induced by CIS in mice. Male NMRI mice were treated with KET (0.4, 0.8, and 1.6 mg/kg, ip) for seven days. On the fourth day of the study, a single dose of CIS (13 mg/kg, ip) was administered, and the mice were sacrificed on the eighth day. The results indicated that administration of KET attenuated CIS-induced elevation of BUN and Cr in the serum, as well as renal KIM-1 levels. This improvement was accompanied by a significant reduction in kidney tissue damage, which was supported by histopathological examinations. Likewise, the decrease in the ratio of GSH to GSSG and antioxidant enzyme activities (CAT, SOD, and GPx), and the increase in lipid peroxidation marker (TBARS) were reversed in KET-treated mice. The ELISA results revealed that KET-treated mice ameliorated CIS-induced elevation in the renal levels of TNF-α, IL-1ß, and IL-18. Western blot analysis exhibited that KET suppressed the activation of the transcription factor NF-κB and the NLRP3 inflammasome in the kidney of CIS-treated mice. Moreover, KET treatment reversed the changes in the protein expression of markers related to apoptosis (Bax, Bcl2, Caspase-3, and p53). Interestingly, KET significantly enhanced the cytotoxicity of CIS in HeLa cells. In conclusion, this study provides valuable insights into the promising effects of KET in mitigating CIS-induced nephrotoxicity.

Nephroprotective effect of diosmin against sodium arsenite-induced renal toxicity is mediated via attenuation of oxidative stress and inflammation in mice.

Arsenic compounds, which are used in different industries like pesticide manufacturing, cause severe toxic effects in almost all organs, including the kidneys. Since the primary route of exposure to arsenic is through drinking water, and millions of people worldwide are exposed to unsafe levels of arsenic that can pose a threat to their health, this research was performed to investigate the nephroprotective effects of Diosmin (Dios), a flavonoid found in citrus fruits, against nephrotoxicity induced by sodium arsenite (SA). To induce nephrotoxicity, SA (10 mg/kg, oral gavage) was administered to mice for 30 days. Dios (25, 50, and 100 mg/kg, oral gavage) was given to mice for 30 days prior to SA administration. After the study was completed, animals were euthanized and blood and kidney samples were taken for biochemical and histopathological assessments. Results showed that SA-treated mice significantly increased the blood urea nitrogen and creatinine levels in the serum. This increase was associated with significant kidney tissue damage in SA-treated mice, which was confirmed by histopathological studies. Furthermore, SA enhanced the amounts of renal thiobarbituric acid reactive substances and decreased total thiol reserves, as well as the activity of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase. Also, in the SA-exposed group, an increase in the levels of kidney inflammatory biomarkers, including nitric oxide and tumor necrosis factor-alpha was observed. The western blot analysis indicated an elevation in the protein expression of kidney injury molecule-1 and nuclear factor-kappa B in SA-treated mice. However, pretreatment with Dios ameliorated the SA-related renal damage in mice. Our findings suggest that Dios can protect the kidneys against the nephrotoxic effects of SA by its antioxidant and anti-inflammatory characteristics.

Diosmin exerts hepatoprotective and antihyperglycemic effects against sodium arsenite-induced toxicity through the modulation of oxidative stress and inflammation in mice.

BACKGROUND: Chronic exposure to high concentrations of inorganic arsenic (NaAsO2) in drinking water is related to an increase in the risk of liver toxicity and diabetes. Diosmin has various pharmacological properties, including antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effects of diosmin on diabetes and hepatotoxicity caused by NaAsO2. METHODS: Sixty male 8-week-old NMRI mice, weighing 25 ± 2 g, were randomly selected and put into six groups. The control (Group 1) was treated orally with distilled water, group 2 was treated with diosmin (100 mg/kg, p.o), group 3 received NaAsO2 (10 mg/kg, p.o), and groups 4, 5, 6 received diosmin (25, 50, 100 mg/kg, p.o), respectively and NaAsO2 (10 mg/kg, p.o). After 29 days, fasting blood sugar (FBS) measurement and glucose tolerance test were done. The mice were sacrificed on day 31, and blood and tissue (liver and pancreas) samples were taken. Then, serum and tissue samples were studied for biochemical and histological evaluations. RESULTS: The results demonstrated that diosmin ameliorated glucose intolerance and decreased FBS compared to the NaAsO2 group. Diosmin (50 and 100 mg/kg) improved the serum factors of liver function (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) in the groups receiving NaAsO2. Moreover, increased levels of nitric oxide, tumor necrosis factor-alpha, and thiobarbituric acid reactive substances in liver tissue induced by NaAsO2 were diminished by diosmin treatment. Administration of diosmin increased total thiol and enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase in liver tissue. Furthermore, treatment with diosmin reduced the increase in protein amount of Sirtuin 3 and nuclear factor kappa B in the groups receiving NaAsO2. Also, the liver and pancreas histological lesions induced by NaAsO2 were attenuated by diosmin treatment. CONCLUSION: Diosmin has a preventive effect against hepatotoxicity and diabetes induced by NaAsO2 in mice through its antioxidant and anti-inflammatory properties.

The role of l -arginine/NO/cGMP/K ATP channel pathway in the local antinociceptive effect of berberine in the rat formalin test.

Berberine is an isoquinoline alkaloid naturally produced by several types of plants. Berberine has extensive pharmacological effects, such as anti-diabetic, anti-inflammatory, and antioxidant effects. In the current study, we assess the antinociceptive effects of berberine and its association with the l -arginine ( l -Arg)/NO/cGMP/K ATP channel pathway via intraplantar administration in rats. To examine the antinociceptive properties of berberine, the formalin test was conducted. The number of rat paw flinches was counted for an h. l -Arg (precursor of nitric oxide, 3-30 µ g/paw), l -NAME (NO synthase inhibitor, 10 and 100 µ g/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200 µ g/paw), and glibenclamide (ATP-sensitive potassium channel blocker, 10 and 30 µ g/paw) were locally injected, respectively, into the right hind paws of rats as a pre-treatment before berberine injection to understand how the l -Arg/NO/cGMP/K ATP pathway plays a role in the antinociceptive effect of berberine. The ipsilateral injection of berberine into the right paw (0.1-10 0 µ g/paw) showed a dose-dependent antinociceptive effect in both the first and second phases of the formalin test, almost similar to morphine (25 µ g/paw). Intraplantar injection of l -Arg (30 µg/paw) increased the antinociceptive effect of berberine in the second phase. In addition, injection of l -NAME, methylene blue, and glibenclamide caused a reduction in the antinociceptive effect of berberine throughout the second phase in a dose-dependent manner. However, the antinociceptive effects of berberine in the first phase of the rat formalin test were not affected by this pathway. As a novel local antinociceptive agent, berberine can exert a peripheral antinociceptive effect via the l -Arg/NO/cGMP/K ATP channel pathway.