Samy Mohamed

Background:
Imatinib mesylate (IM) has been shown to be highly efficacious in the treatment of Chronic Myeloid Leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes. There is a considerable variability in the level of molecular responses achieved with IM therapy. These differences could result from variable drug level which may be due to genetic factors.

The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter responsible for active uptake of IM into CML cells.

Aims:
We hypothesized that the SNPs of this gene could predict the outcomes of IM therapy in CML patients.

Methods:
Fifty patients with CML at chronic phase were studied. All patients were monitored at outpatient clinic of the National Cancer Institute, Cairo University, Egypt. The study was approved by the NCI Ethical Committee for Clinical Research. Written Informed consent was obtained. The polymorphism of SLC22A1 gene was studied using PCR-RFLP technique. Imatinib mesylate level was determined using HPLC-massspectroscopy.

Results:
The mean IM trough plasma level in patients who achieved unfavorable response (n = 25) was 1019 ± 638 ng/mL, and in patients who achieved favorable response (n = 25) 1353 ± 611 ng/mL (p = 0.04).

In regard to SLC22A1 rs(628031) gene, heterogeneous & variant allele (GA&AA) was significantly correlated to unfavorable response while wild allele GG is linked to favorable response(p = 0.0006).

No significant correlation was detected between SLC22A1 gene polymorphism and drug level (p = 0.08).

BACKGROUND/AIM: The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO2) in mice liver.

METHODS: The in vitro cytotoxic effect of nano-sized anatase TiO2 (21 nm) on hepatic cell lines (HepG 2) was investigated. Additionally, n-TiO2 was orally administered (150 mg/kg/day) for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month.

RESULTS: n-TiO2 induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic total antioxidant capacity (TAC) and nitrite/nitrate (NOx) levels. Meanwhile, glutathione-S-transferase (GST) activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO2 significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-β1) and Smad-2, as well as vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced these results.

CONCLUSION: Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO2-induced liver toxicity.

The objective of this study was undertaken to evaluate the protective effect
of Ginger extract either alone or in combination with Rosiglitazone and
Glimepiride on serum Glucose, Triglycerides, Cholesterol ,AST, ALT, γ-GT,
as well as liver Malondialdehyde, Catalase (CAT), Superoxide Dismutase
(SOD), reduced Glutathione (GSH) and lysosomal enzymes ;Acid
phospahtase (ACP), β-D-galactosidase (β-GAL) and N-acetyl-β-Dglucosaminidase

(β-NAG), in streptozotocin-induced diabetic rats. The
animals were divided into seven groups: control normal animals (CN),
control untreated diabetic animals (CD) in which experimental
hyperglycemia were induced by single intraperitoneal injection of
streptozotocin (40mg/kg body mass). The other 5 diabetic groups were
treated orally for 30 days with Rosiglitazone (D/Rosi) (0.8 mg/kg b.w),
Glimepiride (D/Glim) (0.8 mg/kg of b.w), Ginger extract (D/G)(500 mg/kg
of body mass), combination of Glimepiride and Ginger extract (D/Glim+G)
and combination of Rosiglitazone and Ginger (D/Rosi+G) starting 24 hours
after streptozotocin injection. The antioxidant effect of the Ginger extract
was compared with Rosiglitazone and Glimepiride, well-known
hypoglycaemic drugs. The diabetic rats exhibited lowered hepatic GSH
content and CAT, SOD activities associated with elevated levels of hepatic
MDA, liver functions enzymes and lysosomal enzymes as compared with
normal rats. In contrast ginger treatment exerts a therapeutic protective effect
in diabetes by decreasing oxidative stress, liver functions enzymes,
lysosomal enzymes and hepatic damage. Ginger extracts showed an
encouraging hypoglycemic, hypolipaemic, as well as antioxidant properties

and could be considered as a valuable candidate in the reversal of the
complication of diabetes.