Zinc Chloride Enhances the Antioxidant Status, Improving the Functional and Structural Organic Disturbances in Streptozotocin-Induced Diabetes in Rats.

Background and Objectives: Diabetes mellitus (DM) is a complex disease affecting the whole metabolic balance of the body and resulting in multiple organ complications: cardiovascular, neuronal, renal, etc. Our study focuses on investigating the effect of zinc chloride (Zn) on certain blood parameters suggestive for assessing the metabolic disturbances, the liver and kidney function, the oxidative stress and the immune defense capacity in experimental-induced DM with streptozotocin (STZ) and cholesterol in rats. Materials and Methods: The animals were assigned to three groups, as follows: Group 1 (Control): buffer citrate solution 0.1 mL/100 g body; Group 2 (STZ): 20 mg/kg body STZ and fat diet (10 g cholesterol/100 g diet); Group 3 (STZ+Zn): 20 mg/kg body STZ + 5 mg/kg body Zn chloride and the same fat diet. DM was induced by administering STZ in a single take daily, for three consecutive days, Zn and citrate buffer were administered orally for a month. The protocol was approved by the Ethics Committee of the University 'Grigore T Popa' Iasi, in agreement with the International Regulations about the handling of laboratory animals. Results: The use of STZ in rats fed with cholesterol was correlated with important weight gain, hyperglycemia, the intensification of the transaminases activity and the increase in serum alkaline phosphatase, cholesterol, triglyceride, urea, creatinine and in malondialdehyde. Conclusions: The treatment with Zn resulted in weight loss and a decrease in blood sugar in diabetic rats. Supplementation with Zn notably reduced oxidative stress, preserved the pancreatic architecture and restored the liver and kidney function and structure in STZ-induced DM in rats.

Clinical Parameters Affecting the Therapeutic Efficacy of SGLT-2-Comparative Effectiveness and Safety of Dapagliflozin and Empagliflozin in Patients with Type 2 Diabetes.

(1) Background. We aimed to assess long-term efficacy and safety in inadequately controlled type 2 diabetes (T2DM) of two SGLT-2 inhibitors: empagliflozin (Empa) and dapagliflozin (Dapa), combined with metformin, other oral antidiabetics or insulin, according to the protocols in Romania. (2) Methods. The data of 100 patients treated for T2DM with associated dyslipidemia and/or cardiovascular diseases at the University Hospital and Consultmed Medical Center in Iasi were retrospectively reviewed (2017-2021). In total, 48 patients had received dapagliflozin (10 mg with oral antidiabetics or insulin) and 52 patients received empagliflozin (10 mg /25 mg with oral antidiabetics). (3) Results. In both groups, the lowering of BMI was significant: Dapa group (32.04 ± 4.49 vs. 31.40 ± 4.18 kg/m2; p = 0.006), and Empa group (34.16 ± 5.08 vs. 33.17 ± 4.99 kg/m2; p = 0.002). Blood sugar average levels decreased significantly (170 vs. 136 mg/dL; p = 0.001 for Dapa; 163 vs. 140 mg/dL; p = 0.002 for Empa) and also average levels of HbA1c (7.90% vs. 7.51%; p = 0,01 for Dapa; 7.72% vs. 7.35%; p = 0.004 for Empa). (4) Conclusions. Better results in all variables were observed in younger male patients with a shorter duration of diabetes and threshold BMI levels of 34.1, treated with SGLT2, and more significantly with Empa.

Biocompatibility and Pharmacological Effects of Innovative Systems for Prolonged Drug Release Containing Dexketoprofen in Rats.

The present study reports on the in vivo biocompatibility investigation and evaluation of the effects of liposomes containing dexketoprofen in somatic sensitivity in rats. METHOD: The liposomes were prepared by entrapping dexketoprofen in vesicular systems stabilized with chitosan. The in vivo biocompatibility was evaluated after oral administration in white Wistar rats: Group I (DW): distilled water 0.3 mL/100 g body weight; Group II (DEX): dexketoprofen 10 mg/kg body weight (kbw); Group III (nano-DEX): liposomes containing dexketoprofen 10 mg/kbw. Blood samples were collected from caudal lateral vein one day and seven days after the substance administration, to assess the eventual hematological, biochemical, and immunological changes. The investigation of somatic pain reactivity was performed using the hot plate test, to count the latency time response evoked by the thermal paws' noxious stimulation. RESULTS: Original liposomes entrapping dexketoprofen, with mean size of 680 nm and good stability, were designed. Laboratory analysis indicated no substantial variances between the three treated groups. The treatment with liposomes containing dexketoprofen resulted in a prolongation of the latency time response, statistically significant in the interval between 90 min and 10 h, in the hot plate test. CONCLUSIONS: The use of liposomes with dexketoprofen proved a good in vivo biocompatibility in rats and prolonged analgesic effects in the hot plate test.

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice.

Background and Objectives: The selective kappa opioid receptor agonist U50,488 was reported to have analgesic, cough suppressant, diuretic and other beneficial properties. The aim of our study was to analyze the effects of some original chitosan-coated liposomes entrapping U50,488 in somatic and visceral nociceptive sensitivity in mice. Materials and Methods: The influence on the somatic pain was assessed using a tail flick test by counting the tail reactivity to thermal noxious stimulation. The nociceptive visceral estimation was performed using the writhing test in order to evaluate the behavioral manifestations occurring as a reaction to the chemical noxious peritoneal irritation with 0.6% acetic acid (10 mL/kbw). The animals were treated orally, at the same time, with a single dose of: distilled water 0.1 mL/10 gbw; 50 mg/kbw U50,488; 50 mg/kbw U50,488 entrapped in chitosan-coated liposomes, according to the group they were randomly assigned. Results: The use of chitosan-coated liposomesas carriers for U50,488 induced antinociceptive effects that began to manifest after 2 h, andwere prolonged but with a lower intensity than those caused by the free selective kappa opioid in both tests. Conclusion: In this experimental model, the oral administration of nanovesicles containing the selective kappa opioid agonist U50,488 determined a prolonged analgesic outcome in the tail flick test, as well as in the writhing test.

The effects of magnesium nanovesicle formulations on spatial memory performance in mice.

AIM: The study investigates the effects of magnesium nanovesicles on the memory processes performance in mice. MATERIALS AND METHODS: L-a-phosphatidylcholine was used to obtain nano formulations as lipid vesicles systems stabilized thereafter with chitosan. The experiment was carried out on white Swiss mice, divided into 3 groups of 7 animals each, treated orally 7 consecutive days: Group I (Control): 0.1 mL/10g distilled water; Group II (Mg): 1 mmol/kbw magnesium chloride; Group III (Mg-vesicles): 1 mmol/kbw magnesium nanovesicles. The spatial memory performance was assessed by recording spontaneous alternation behavior in Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during a single 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed according to the formula: (number of alternations/total number of arm visits--2) x 100. Data were analyzed using SPSS 17.0 software. Experimental protocols were implemented according to the recommendations of the University Committee for Research and Ethical Issues. RESULTS: New carrier formulations entrapping magnesium chloride were designed: their mean size was 129.56 nm and the mean Zeta potential was +36.1 mV, indicating a moderate stability of the solution. Oral administration of magnesium vesicles resulted in a significant increase of spontaneous alternation percent in Y-maze test (p < 0.01), which suggests an improvement of short-term memory. CONCLUSIONS: Using magnesium chloride entrapped in lipid vesicles induced an enhancement of cognitive functions in mice especially by facilitation of learning extinction.

Synergic effects of pregabalin-acetaminophen combination in somatic and visceral nociceptive reactivity.

BACKGROUND/AIMS: The present study investigates the effects of pregabalin (PGB), acetaminophen (ACET) and tenoxicam (TNX) administration in somatic and visceral nociception, using the tail flick test and the writhing test in mice. METHODS: In the tail flick test, the substances were administered orally and the latency time response was recorded 15, 30, 60, 90 and 120 min after administration. In the writhing test, pain responses were scored every 5 min during a 30-min period after intraperitoneal injection of diluted acetic acid. RESULTS: Our study demonstrated that oral administration of the combination PGB-ACET resulted in a stronger increase of latency reaction - statistically significant after 15 min compared to TNX and after 30 min compared to PGB in tail flick test. In the writhing test, the combination PGB-ACET, but also PGB-TNX, resulted in a stronger decrease of writhe numbers - statistically significant compared to the effects of the separate administration of each substance. This decrease was more intense in animals treated with the combination PGB-ACET than with PGB-TNX. CONCLUSION: These results suggest an antinociceptive activity which may be a consequence of the synergic action of the substances.