The limited usage of doxorubicin in chemotherapy returns to its toxicity on different organs. Thyme oil has antioxidant, antiinflammatory, and anticancer activities. This study aimed to investigate the alleviative effect of thyme oil on doxorubicininduced hepatotoxicity in rats. Twenty adult female albino rats (Rattus norvegicus) were randomly divided into four groups (5 rats/group): control group, thyme group received orally 0.5 mL thyme oil/kg body weight once/week for 6 consecutive weeks, doxorubicin group received intraperitoneally 2 mg doxorubicin/kg body weight once/week for 6 consecutive weeks, and "doxorubicin+thyme" group received both doxorubicin and thyme oil once/week for 6 consecutive weeks. Alteration in the liver ultrastructure and changes in the activities of serum aminotransferases and antioxidant enzymes were estimated in the current study. Liver histology of doxorubicin-treated rats showed congested blood vessels, masses of inflammatory leucocytic infiltration, and cytoplasmic vacuolation and pyknotic nuclei of the liver cells. Liver ultrastructure of doxorubicin-treated rats showed vacuolated and rarified cytoplasm, enlarged ruptured mitochondria, and large number of lysosomes. The rough endoplasmic reticulum lost most of its ribosomes, and its cisternae were unparalleled, as well as the nuclear envelope was mild tortuous. In addition, the aminotransferases (ALT and AST) activities and MDA level were increased significantly; while the antioxidant enzymes (SOD and CAT) activities were decreased significantly in the doxorubicin-treated animals compared with the control group. In the current study, thyme oil ameliorated most of the hepatotoxic effects of doxorubicin in rats. Therefore, thyme oil can be used as adjunct therapy to reduce doxorubicin toxicity.
Background
Hepatitis C is a liver infection caused by the hepatitis C virus (HCV). It can cause both acute and chronic hepatitis. Sofosbuvir (sofo) is a nucleotide analog inhibitor of HCV NS5B polymerase used to treat chronic hepatitis C infection as a component of a combination of antiviral treatment regimen. Many side effects of sofo were reported in different mammalian organs including kidney. Moringa oleifera (MO) is one of the medicinal plants which have many pharmacological activities and nutritional applications due to its rich phytonutrients content. This study aimed to investigate the possible ameliorative effect of MO seed oil against nephrotoxicity induced by sofo in adult male albino rats. The experimental animals were divided equally into four groups. Group I: animals were served as control. Group II: animals were orally given MO oil (2 ml/kg/day). Group III: animals were orally administered with sofo (36 mg/kg/day). Group IV: animals were orally given sofo then after 2 h they were given MO oil (with the same previous doses). All doses were daily given to the animals for eight weeks. At the end of the experiments, animals were sacrificed and sera were collected to determine urea, creatinine and malondialdehyde levels and catalase activity. Kidneys were removed out and prepared for both the histological and immunohistochemical studies.
Results
Sofo-treated animals showed many pathological changes; damaged glomeruli and degenerated renal tubules with vacuolated lining epithelial cells contain pyknotic nuclei. In addition, leukocytic infiltration, congested blood vessels and hemorrhage were seen. Caspase-3 and PCNA were expressed in a large number of cells in the same group. Moreover, a significant increase in urea, creatinine and malondialdehyde levels was recorded as well as a significant decrease in catalase activity. Co-treatment of MO oil with sofo effectively counteracted the observed adverse effects. It attenuated the histological picture of the kidney, significantly ameliorated urea, creatinine and malondialdehyde levels and catalase activity and restored the normal expressions of caspase-3 and PCNA.
Conclusions
Moringa oleifera oil can ameliorate nephrotoxicity induced by sofo via its antioxidant, anti-inflammatory and anti-apoptotic properties.
The hepatitis C virus (HCV) causes both acute and chronic hepatitis which spread worldwide and accompanied with severe complications in long period of injury. Sofosbuvir (sofo) is a new drug for HCV treatment. Although it has an effective potential in reducing HCV load, its use was accompanied by some side effects. Moringa oleifera (MO) seed oil is natural food-supplemented oil has many pharmaceutical properties which give the plant the ability to reduce or improve the side effects of many insults. This work aimed to determine the possible protective effects of MO seed oil against sofo-nephrotoxicity. Four experimental groups were used; the control group, MO oil group was orally given MO seed oil (2ml/kg/day), sofo group was orally given sofo (36mg/kg/day) and sofo and MO oil group was orally administered sofo, then after 2 hours they were given MO oil. The rats received all doses daily for eight weeks. Twenty four hours following the last injection, rats were anesthetized, sacrificed, the two kidneys were quickly removed and the blood samples were withdrawn for complete blood count (CBC) and determination of the activity of superoxide dismutase (SOD) and the level of glutathione (GSH). Sofosbuvir induced marked ultrastructural changes and significant decrease in SOD activity and GSH level. In addition, CBC of the same groups showed significant decrease in the mean corpuscular value and the mean corpuscular hemoglobin and significant increase in red blood cells count. On the other hand, co-treatment with MO seed oil efficiency improved sofo-induced nephrotoxicity which was evident from the disappearance of most of the ultrastructural changes and improving SOD activity and GSH level. Conclusions: Moringa oleifera seed oil may improve the ultrastructural and biochemical changes associated with nephrotoxicity induced by sofo due to its antioxidant and anti-inflammatory constituents.
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