Sally A. El Awdan

Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study

Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity. Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically. Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA. Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients.

Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin induced toxicity

Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Reconstitutable spray dried ultra-fine dispersion as a robust platform for effective oral delivery of an antihyperlipidemic drug

The current article highlights the application of spray drying technique to produce an ultra-fine powder encapsulating the antihyperlipidemic drug, atorvastatin calcium (ATV). First, ATV was dissolved in an emulsion formulation, and different carriers (pectin, alginate, chitosan HCl and hydroxypropylmethyl cellulose) in two concentrations (1.5 and 3%) were added. Then, these carrier-containing formulations were subjected to spray drying, whereby ultra-fine ATV-loaded spray dried emulsions were produced (ATV-SDE). The optimum formulation; ATV-SDE7 containing 3% w/w pectin was selected showing an obviously enhanced dissolution profile compared to the other used polymers which could be attributed to its lower ability to swell in acidic medium, resulting in faster drug diffusion into release medium. Thus, ATV-SDE7 was subjected to further characterization including; DSC, XRPD, SEM and flowability properties. In-vivo studies were conducted using high-fat induced hyperlipidemic rats. The optimum formulation depicted normal lipid profile showing significant reduction in the measured parameters at the end of daily oral treatment, compared to ATV marketed tablets and control hyperlipidemic rats confirmed by normal liver sections upon histopathological examination. The superior lipid-lowering activity of ATV-SDE7 was not only due to the enhanced dissolution of ATV but also due to the presence of pectin which is capable of lowering both cholesterol and triglyceride serum levels. Hence, the present study suggests that the formulation strategy employing ultrafine redispersible spray dried emulsion with pectin as a carrier holds a promising approach for the development of a novel dosage form of enhanced antihyperlipidemic effect for ATV.

Experimentally designed lyophilized dry emulsion tablets for enhancing the antihyperlipidemic activity of atorvastatin calcium: Preparation, in-vitro evaluation and in-vivo assessment

ABSTRACT This article presents the development of lyophilized orally disintegrating tablets prepared with the dry emulsion technique to enhance the in‐vitro dissolution and in‐vivo performance of the poorly bioavailable drug atorvastatin calcium (ATV). Tablets were fabricated by freeze‐drying o/w emulsions of ATV. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol) and a collapse protectant (glycine) as the water phase and Labrafac® as the oil phase in the presence of surfactant (synperonic® PE/P 84 or synperonic® F108) under proper homogenization. The influence of formulation parameters on friability of the prepared tablets, disintegration time and in‐vitro dissolution of the drug from these tablets were investigated. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In‐vitro dissolution study revealed the enhanced dissolution rate of ATV from the lyophilized dry emulsion tablets (LDET) compared to the plain drug. DSC and XRD studies of the optimized ATV‐loaded LDET proved the presence of the drug in the amorphous form. SEM images showed the intact, porous and non‐collapsible structure of the prepared LDET with complete loss of ATV crystallinity. Administration of ATV‐loaded LDET to high fat diet‐induced hyperlipidemic rats demonstrated a significant decrease (p < 0.05) in the serum and tissue levels of the tested parameters compared to the market product used. The obtained results suggest a promising, easy‐to‐manufacture and effective dosage form for the treatment of hyperlipidemia. Graphical abstract Figure. No Caption available.

Hypoglycemic activity of Gleditsia caspica extract and its saponin-containing fraction in streptozotocin-induced diabetic rats.

Abstract The fruits of Gleditsia species (Fabaceae) have been known in traditional medicine as a saponin-rich herbal medicine. The present study aimed to investigate the effects of the total methanolic extract of Gleditsia caspica (MEGC) and its saponin-containing fractions (SFGC) on hyperglycemia in streptozotocin (STZ)-induced diabetic rats. A single intraperitoneal injection of STZ (55 mg/kg body weight) was used to induce hyperglycemia in male albino rats. MEGC (15, 30 and 60 mg/kg, p.o.) and SFGC (15, 30 and 60 mg/kg, p.o.) were administered to the diabetic rats daily for 14 days. The anti-diabetic drug gliclazide (10 mg/kg, p.o.) was used as a positive control. Blood samples were collected from overnight fasted rats for the evaluation of the antihyperglycemic, antihyperlipidemic and antioxidant activities. The levels of glucose, triglycerides (TG), cholesterol (TC) and malondialdehyde (MDA) were increased significantly, whereas the levels of α-amylase, insulin and reduced glutathione (GSH) were decreased in the experimental diabetic rats. Pancreas and liver of the diabetic rats exhibited significant changes in the histopathology, morphology and DNA content. Administration of MEGC or SFGC led to a decrease in the levels of glucose, TG, TC and MDA. In addition, the levels of α-amylase, insulin and GSH were increased in MEGC and SFGC treated diabetic rats. Also, the histopathological and morphological changes, as well the changes in DNA were significantly reversed by the extracts. Thus, MEGC and SFGC exhibited potent hypoglycemic and hypolipidemic activities in STZ- induced diabetic rats.