Therapeutic benefit of oregano oil in the acute idiosyncratic hepatotoxicity induced by carbon tetrachloride in rats: Adverse effects of high dose of oreganum.

Toxicity caused by carbon tetrachloride (CCl4) can lead to serious liver injury. The aim of the study is to investigate the protective effects of oregano oil (Origanum minutiflorum extract oil) against CCl4-induced liver injury. Two doses of oregano oil were used in the experiment: a low dose (LD; 20 mg/kg) and a high dose (HD; 60 mg/kg) during 2 weeks. CCl4 caused severe liver damage, nucleolus destruction in hepatocytes and cytogenetic changes in the nucleus. Indirectly, CCl4 causes decreased protein synthesis and significantly high creatinine and urea values. Hematological disorders have been recorded, such as decreased RBC and hemoglobin concentration, increased WBC and deformability of the erythrocyte membrane. Both doses of oregano oil had protective effects. Improved protein synthesis and high globulins level, creatinine and urea were found in both groups. Cytogenetic changes in the nucleus of hepatocytes were reduced. A high dose of oregano oil had maximal protective effects for RBC, but a very weak effect on hemoglobin synthesis. Also, WBC and lymphocyte values were low. Origanum stimulates protein synthesis and recovery of hepatocytes after liver injury, reduces the deformability of the erythrocyte membrane. High doses of oregano oil decreased WBC and lymphocytes which may lead to a weakening of the immune response. However, high doses are more effective against severe platelet aggregation than low doses, suggesting an effective treatment against thrombocytosis.

Aronia melanocarpa (Michx.) Elliott 1821 Extract Has Moderate Ameliorative Influence on Biochemical and Hematological Parameters in Gentamicin-Induced Nephropathy in Wistar Rats.

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. Nephrotoxicity refers to the impairments of the kidneys caused by the use of GM and can result in decreased kidney function and in severe cases, kidney failure. Aronia melanocarpa extract (AME), also known as the black chokeberry, has been used for its protective effects on the kidneys. AME concentration of 3.38 mg/kg (max antioxidant activity in vitro) was used to determine its effectiveness against induced nephropathy during 30 days. GM treatment caused significant hypoalbuminemia and high values of globulins, creatinine, and urea compared to the control group. GM application lead to hemolysis occurrence, echinocytosis, and platelets aggregation. Significantly high values of segmented neutrophils and low values of non-segmented neutrophils were recorded in the blood of rats treated with chokeberry extract (AME). In the pre-treatment (AME + GM), severe hypochromic anemia and a significant improvement in hematological parameters, as well as a reduction of anemia in the post-treatment (GM + AME), were noted. Post-treatment AME also significantly regulates urea and creatinine values. Statistically significantly low hemoglobin values were found in all groups treated with AME. Current study suggests that compounds in the AME have a moderate beneficial effect against renal injury and anti-inflammatory properties that may help protect the kidneys from injury caused by GM.

Impact of dietary supplementation with chokeberry (Aronia melanocarpa, Michx.) on tetrachloride-induced liver injury in Wistar rats: Hematological and biochemical implication.

In the current study, we assessed the hematological/biochemical alterations, histopathological changes in the liver, and blood cell disorders in Wistar rats exposed to a toxic concentration of carbon tetrachloride (CCl4 ) and the potential protective effect of a 30-day oral extract of chokeberry (Aronia melanocarpa, AM). The concentration of AM (3.38 mg/kg) obtained by quantitative purification from AM fruit showed the highest antioxidant activity (AOA) in vitro and was used for oral ingestion. In addition to high AOA, high values of total phenols (85.334 mg/g), total phenolic acid (606.95 mg/g), total flavonids (22.10 mg/g), and total anthocyanins (11.01 mg/g) were recorded in chokeberry extract. CCl4 treatment caused serious liver injury, hepatocyte and blood cell impairment. AM extract given to rats before CCl4 application had a moderate hepatoprotective effect in comparison to after CCl4 application. White blood count and leukocytes were significantly altered by CCl4, however, the protective role of AM in leukocyte disorders was not established. A high number of microcytes, stomatocytes, anisocytes, and hemolyzed erythrocytes during CCl4 exposure was reduced by AM extract. Flower erythrocytes in the AM + CCl4 group were recorded. Supplementation with chokeberry extract without CCl4 caused hyperproteinemia and hyperalbuminemia. Although the results indicate a weak protective role for AM, it is nevertheless important for improved erythropoiesis and regulation of the development of anemia. The hepatoprotective role of AM was moderate, and the immune response was not proven. Daily consumption of chokeberry extract can improve health. However, the results of our study showed that the ingestion of AM extract at this dose with the highest AOA would have more effective effects if the supplementation were significantly increased.

L-cysteine protective effects against platelet disaggregation and echinocyte occurrence in gentamicin-induced kidney injury.

Gentamicin (GM) is an aminoglycoside antibiotic that induces nephrotoxicity. GM also causes necrosis of cells in the renal proximal tubules, resulting in acute tubular necrosis, followed by acute renal failure. Morphological alteration of blood cells, leukocytes and platelets count, as well as biochemical effects of L-cysteine (Cys) and antibiotic gentamicin, in clinically healthy male Wistar rats, were studied. Rats were divided into four groups: control (injected with 0.9% saline i.p.), GM (80 mg/kg b.w.; gentamicin injected i.p.), Cys-GM (100 mg/kg b.w.; L-cysteine and 80 mg/kg b.w. gentamicin injected i.p.), and Cys-GM-Cys (administered double dosage of 100 mg/kg b.w. L-cysteine and 80 mg/kg b.w. gentamicin i.p.). Biochemical and hematological analyses were performed on blood samples taken six days after treatments. Total proteins, albumin concentration and A/G ratio were significantly lower in experimental groups. Cholesterol, triglycerides, urea, and creatinine concentrations were significantly higher in relation to control. GM-induced lymphocytopenia, thrombocytopenia and neutrophilia. Echinocytosis and platelet disaggregation were found in all GM-treated animals. GM caused renal injury which indirectly led to erythrocyte abnormalities, changes in platelet aggregation, decreased protein fractions, and increased lipid and nitrogen components. The results suggest that GM-induced renal injury leads to significant biochemical changes in blood plasma, erythrocyte membrane impairment which can consequently cause anemia. Therefore, Cys might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced renal injury and blood cell disorders.

Protective role of the dandelion extract against the blood-liver axis, cell membranes, and anemia disorder in sodium benzoate-exposed rats.

Sodium benzoate (SB) as an additive in various food products prevents the growth of microbes. Although SB is considered safe, many studies have reported adverse effects. The aim of this study was to investigate the effect of dandelion extract on cell damage and hematological and biochemical disorders induced by SB in male albino rats. Different doses of SB (200 and 600 mg/kg) and ethanolic dandelion root extract (D) (40 mg/kg) were used in a 2-week treatment of rats. Rat mortality and a higher frequency of behavioral alterations such as apathy, anxiety, and aggression have been reported at a higher dose of SB. Changes in urine pH, proteinuria, nitrituria, and bilirubinemia caused by SB were regulated by adding dandelion extract. Analysis of specific serum and urine parameters, as well as microscopic analysis of hepatocytes, showed liver and kidney failure. Anemia associated with hemolytic disorder due to erythrocyte impaired the presence of acanthocytes, and decreased values of erythrocyte blood count, hemoglobin concentration, average red blood cell size, hemoglobin amount per red blood cell, and mean corpuscular hemoglobin concentration were caused by SB treatment. As a dietary supplement, dandelion extract can be useful in the prevention of SB-induced liver and kidney injury, and also a remedy against induced anemia, neutropenia, thrombocytopenia, hyperproteinemia, hyperglycemia, and reduction of inflammatory responses.

Protective role of antithrombin III in suppressing acute responses in a rat model of renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (IR) produces-induced injury and is characterized by restriction of blood supply to the kidney followed by restoration and re-oxygenation of the tissue. IR injury in the kidney contributes to pathological processes known as acute renal injury (ARI). Ischemia-perfusion injury (IRI) of the left renal artery has been demonstrated in Wistar rats. A total of 32 animals were divided into four groups: control group (SHAM), IR animals with induced ischemia-reperfusion, AT-IR animals treated by antithrombin III (AT) before IR, and AT-IR-AT animals with AT administered before and after IR. IR-induced hyperproteinemia, hyperalbuminemia, hyperglobulinemia, and a significantly low A/G ratio. Exogenous administration of AT prior to IR development effectively regulates protein fraction levels by establishing normoproteinemia. The preventive effect of AT regulates serum protein levels and reduces acute inflammation by reducing globulin and establishing physiological levels of A/G ratios. The therapeutic effect of AT given after IR is not effective compared to AT administered before IR. Protein fractions can serve as an important predictive marker for the prognosis and duration of acute inflammation. Serum globulin levels and the A/G ratio may serve as effective prognostic markers in acute inflammation caused by ischemia-reperfusion injury of the kidney. A strong correlation between globulin and the A/G ratio suggests novel markers associated with acute inflammation that can lead to chronic kidney disease.

Evaluating the effects of anticoagulant rodenticide bromadiolone in Wistar rats co-exposed to vitamin K: impact on blood-liver axis and brain oxidative status.

The aim of this study was to investigate the beneficial effects of vitamin K relate to protection against detrimental effects of bromadiolone. Wistar rats (n = 30) were divided in three groups (n = 10): control group and two groups treated with bromadiolone (0.12 mg/kg) and bromadiolone + vitamin K (0.12 mg/kg + 100 mg/kg) over the period of four days. The main findings in the bromadiolone-exposed rats, such as damaged hepatocytes, high levels of globulin, total proteins and lymphocytes, and altered albumin/globulin ratio, collectively indicate an acute inflammatory process. Morphological changes in erythrocytes include microcytosis, hypochromia, hyperchromia, hemolysis, stomatocytosis, and spherocytosis. Significantly low values of RBC, Hct, and hemoglobin concentrations indicate impairments of the hematopoietic pathway causing combined anemia. The selected dose of bromadiolone caused a non-significant increase of catalase activity and a significant increase of the total protein content in brain tissue homogenates. Vitamin K supplementation reduced many of the harmful effects of bromadiolone. The cytoprotective role of vitamin K was proved to be of great importance for the preservation of structural changes on the membranes of hepatocytes and erythrocytes, in addition to the known role in the treatment of coagulopathies. The results of the study suggest valuable properties of vitamin K in the prevention and treatment of various types of anemia caused by bromadiolone toxicity. Future research is necessary to determine the adequate dose and treatment duration with vitamin K in disorders caused by the cumulative action of bromadiolone and possibly other pesticides.

Vitamin D3 attenuates oxidative stress and regulates glucose level and leukocyte count in a semi-chronic streptozotocin-induced diabetes model.

PURPOSE: Vitamin D3 (vit-D3) is a potent immunomodulator with anti-inflammatory and antioxidative properties. We used streptozotocin (STZ)-induced rat model of diabetes (DM) to evaluate the effects of vit-D3. We measured serum biochemical parameters, interleukin-17 (IL-17), osteocalcin (OC), malondialdehyde (MDA), and immune cell count on the 21st day of experiment. METHOD: A total of 24 Wistar rats were randomly divided into three groups. Each group had eight rats. During the 1st day of the experiment, the control group was injected intraperitoneally with citrate buffer, while STZ group and STZ + vit-D3 group were injected by a single i.p. dose (35 mg/kg) of STZ dissolved in citrate buffer (pH 4,5; 0,1 M). Vitamin D3 was applied via oral gavage once daily to the STZ + vit-D3 group for a total period of 14 days, starting from the 7th day of the experiment. RESULTS: STZ rats showed a significant reduction in OC and an increase in MDA and IL-17 serum concentrations compared to the control rats. We also observed a significant STZ-associated decrease in the number of lymphocytes and a significant increase in monocyte and eosinophil number. Oral treatment with vit-D3 to STZ-induced diabetic rats significantly increased OC and decreased MDA serum levels. Furthermore, vit-D3 treatment resulted in a good regulation of hematopoiesis such as increase in the number of segmented granulocytes and lymphocytes and a reduction in the number of monocytes and eosinophils. CONCLUSION: Vit-D3 treatment has important therapeutic effects; among many others it can attenuate oxidative stress and ameliorate the hyperglycemic state in the STZ-induced rat diabetic model, which is promising for further clinical trials.