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1.
Tissue Cell ; 89: 102439, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38889555

ABSTRACT

Hydroxychloroquine (HCQ), an antimalarial drug widely used in treating rheumatoid disorders. Many side effects have been reported with HCQ administration indicating its hazardous effects on various organs. No previous studies reported the effect of long-term administration of oral HCQ on pancreatic tissue. Our study assessed pancreatic tissues functional and histopathological alterations following prolonged oral administration of HCQ. We also investigated the possible ameliorative effects of the lactoferrin (LF) coadministration with HCQ in adult male albino rats. Forty adult male Wister albino rats were divided into: negative control, LF positive control (2 g/kg), HCQ-treated (200 mg/kg), and HCQ+LF treated. Biochemical, histological, immunohistochemical, and morphometric analyses of the pancreatic tissues were conducted. Our findings revealed that prolonged oral administration of HCQ induced significant disruption of the pancreatic acinar architecture, enlarged congested islets of Langerhans, and elevated plasma insulin, amylase, and lipase levels. Interestingly, LF administration ameliorated the deleterious effects of prolonged HCQ administration on pancreatic tissue of adult male albino rats. In conclusion, prolonged oral administration of HCQ induced pancreatic tissue damage in rats, while LF attenuates HCQ-induced pancreatic injury. Our results emphasized the necessity of prescribing HCQ with caution, considering both dosage and treatment duration.

2.
Cureus ; 15(3): e35736, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37016650

ABSTRACT

Background Diabetic nephropathy is a severe condition that causes persistent kidney problems and chronic renal failure. Rosemary (Rosmarinus officinalis L) is widely recognized for its antioxidant, antidiabetic, anti-inflammatory, antithrombotic, hepatoprotective, and anticancer activities. The current study evaluated rosemary essential oil (REO) effects on biochemical, histological, and immunohistochemical kidney alterations in streptozotocin (STZ)-induced diabetic rats and compared these effects with those of insulin and both combined. Methods We randomly distributed 36 adult albino rats into 6 groups: normal control (non-diabetic), diabetic (streptozotocin, 55 mg/kg, intraperitoneal), diabetic insulin-treated (Lantus insulin 2 units/day, SC), diabetic REO-treated (REO, 10 ml, nasogastric gavage), and diabetic insulin & REO-treated groups. Biochemical, histological, and immunohistochemical analyses were conducted. Results The diabetic group revealed a substantial increase in blood glucose, urea, creatinine, and uric acid, as well as malondialdehyde (MDA) and catalase (CAT) concentrations in kidney homogenates, high score of tubular injury, and increased glomerulosclerosis, along with marked reduction of total glutathione (GSH) and superoxide dismutase (SOD) when compared to control. Evident improvement was detected in rats treated with REO as it demonstrated antioxidant, anti-inflammatory, anti-apoptotic, pro-proliferative, and mild anti-hyperglycemic effects on diabetic rats, reducing the kidney damage caused by diabetes. Combined insulin and REO restored normal blood glucose, renal excretory function tests, antioxidant markers, and renal cortex histology. Conclusion The data presented in the current study's in vivo animal model suggests that REO supplementation has beneficial nephroprotective effects on the structural and, to a lesser extent, functional levels of diabetic rats. Furthermore, the detected nephroprotective effects of insulin and REO combined are superior to those of either administered alone. However, further studies are needed to evaluate these conclusions in humans further.

3.
Life Sci ; 319: 121496, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36822315

ABSTRACT

AIMS: Ehrlich ascites carcinoma and its subcutaneous inoculated solid tumour form (SEC) are reliable models for chemotherapeutic molecular targets exploration. Novel chemotherapeutic approaches are identified as molecular targets for intrinsic apoptosis, like the modulation of the second mitochondria-derived activator of caspases (SMAC). SMAC is a physiological substrate of mitogen-activated protein kinases (MAPKs). Glutathione-S-transferase P1 (GSTP1) and its close association with MAPKs play an important role in malignant cell proliferation, metastasis, and resistance to chemotherapeutics. Nitazoxanide (NTZ) is an emerging cancer therapy and its targeted GSTP1 evidence remains a knowledge need. MAIN METHODS: In the present mice-established SEC, the chemotherapeutic roles of oral NTZ (200 mg/kg/day) and 5-fluorouracil (5-FU; 20 mg/kg/day, intraperitoneally) regimens were evaluated by measuring changes in tumour mass, the tumour MAPKs, cytochrome c, Bcl-2 interacting mediator of cell death (BIM), and SMAC signalling pathway in addition to its molecular downstream; caspases 3 and 9. KEY FINDINGS: Computational analysis for these target protein interactions showed direct-ordered interactions. After individual therapy with NTZ and 5-FU regimens, the histological architecture of the extracted tumour discs revealed decreases in viable tumour regions with significant necrosis surrounds. These findings were consistent with gross tumour sizes. Each separate regimen lowered the remarkable GSTP1 and elevated the low MAPKs expressions, cytochrome c, BIM, SMAC, and caspases 3, and 9 in EST tissues. SIGNIFICANCE: The chemotherapeutic activity of NTZ in SEC was proven. Additionally, NTZ possesses a SMAC modulatory activity that, following thorough research, should be taken into consideration as a chemotherapeutic approach in solid tumours.


Subject(s)
Carcinoma , Caspases , Animals , Mice , Caspases/metabolism , Apoptosis Regulatory Proteins/metabolism , Glutathione Transferase , Cytochromes c/metabolism , Cell Line, Tumor , Apoptosis , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Mitochondria/metabolism , Mitogen-Activated Protein Kinases , Computational Biology , Mitochondrial Proteins/metabolism
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