Comparison of formulation characteristics of drugs and dietary supplements containing alpha-lipoic acid relevant to therapeutic efficacy.

OBJECTIVE: Healthcare professionals lack the knowledge about the impact of formulations on treatment effectiveness. This is further complicated by the existence of dietary supplements containing the same active pharmaceutical ingredients (API) as drug formulations [e.g., alpha-lipoic acid (ALA)], to which the strict formulation testing requirements do not apply. This research aimed to compare ALA-containing drugs and dietary supplements through the determination of uniformity of content, disintegration time and dissolution rates. MATERIALS AND METHODS: A total of seven different ALA formulations (5 dietary supplements, 2 drugs) were tested for uniformity of content, disintegration time and dissolution rates. All tests were performed in accordance with the 10th European Pharmacopoeia. ALA was determined spectrophotometrically. RESULTS: Uniformity of content testing revealed larger variations of ALA content in three formulations of dietary supplements. Dissolution curves generated at 50 and 100 rpm differed significantly. Testing requirements were met only by one dietary supplement at 50 rpm, and one drug and two dietary supplements at 100 rpm. Disintegration testing showed limited impact on the release kinetic of ALA, as opposed to formulation type. CONCLUSIONS: Considering the lack of regulation on dietary supplement formulations and the variable success of them conforming to pharmacopoeial requirements, it is an imperative for stricter regulations on the dietary supplements' formulations to be imposed globally.

Impact of winter savory extract (Satureja montana L.) on biochemical parameters in serum and oxidative status of liver with application of the principal component analysis in extraction solvent selection.

OBJECTIVE: Satureja montana L. is traditionally used as spice and for treatment various diseases. Many studies have shown antioxidative effect of Satureja species. Our thorough study in an animal model was performed through measurement of biochemical parameters in the serum, histology analysis and determination of oxidative status of the liver, coupled with investigation of extraction solvent selection using principal component analysis (PCA). MATERIALS AND METHODS: Winter savory dry extract (500 mg/kg) dispersion and saline solution were given to Wistar rats for 7 days after exposure to oxidative stress using toxic doses of paracetamol (600 mg/kg). Rats were sacrificed, after which a complete autopsy was performed, the blood obtained was used to determine biochemical parameters, and the liver was sliced for histological analysis and determination of oxidative stress enzymes. RESULTS: Indicators of hepatic and kidney functions, as well as the concentration of oxidative stress enzymes, were statistically significantly lower in animals treated with Satureja montana L. extract compared to the paracetamol group alone before the toxic dose of paracetamol. Liver enzymes were unaltered by pre-treatment with the extract, but the level of lipid peroxidase was decreased, and the level of catalase, glutathione reductase and superoxide dismutase increased proving in vivo antioxidant effect. In addition, the number of inflammatory cells is decreased coupled with activity of CYP2E1 enzymes proving hepatoprotective effect. CONCLUSIONS: Satureja montana L. extract in our research has shown hepatoprotective, anti-inflammatory and antioxidative effect. PCA analyses indicated that extraction mediums have a great impact on the antioxidative effect.

Acute toxic effects of single dose dacarbazine: hematological and histological changes in an animal model.

Treatment of advanced soft tissue sarcoma usually includes dacarbazine (DTIC), an alkylating agent that methylates DNA and is active during all phases of the cell cycle. Common side effects of DTIC include nausea, vomiting, impaired liver and kidney function, myelosuppression, and pneumonia. There are no accounts, however, of histological and hematological changes caused by DTIC. We investigated acute hematological and morphological changes in different organs and in tumors that were caused by a single dose of DTIC. Adult Syrian golden hamsters were inoculated with a suspension of tumorigenic baby hamster kidney (BHK) cells by subcutaneous injection. On day 14 after inoculation, doses of 1.4, 1.6, 1.8 or 2.0 g/m(2) DTIC were injected intraperitoneally into the hamsters. Hamsters in the control group were injected with physiological saline in the same way. Seven days after drug or saline injection the animals were sacrificed and samples of blood, heart, kidney, liver, lungs, spleen, small intestine and tumor were excised, processed and analyzed. Mitoses were counted using an ocular extension with engraved frame. Anemia, thrombocytopenia and leukocytosis were found in the control group of hamsters with fibrosarcoma, whereas animals with fibrosarcoma treated with DTIC developed anemia, thrombocytopenia and leukopenia. Severe pneumonia and moderate hepatitis were detected in all DTIC treated groups. Effects of DTIC on tumor cells included rounding and enlargement of nuclei and rarefaction of chromatin. The number of mitoses was reduced with increasing doses of DTIC. Hepatitis, myelosuppression, pneumonia, and dose-related inhibition of tumor cell proliferation were observed after a single dose of DTIC.