Hypericum perforatum L. treatment restored bone mass changes in swimming stressed rats.

UNLABELLED: Stress, via corticosteroids release, influences bone mass density. Hypericum perforatum (Hp) a traditional remedy possess antidepressive activity (serotonin reuptake inhibitor) and wound healing properties. Hp preparation contains mainly hypericin, hyperforin, hyperoside and flavonoids exerting oestrogen-mimetic effect. Cold swimming represents an experimental model of stress associating mental strain and corporal exhaustion. OBJECTIVES: This study investigates the Hp effect on femur and mandible bone mass changes in rats under cold forced swimming procedure. METHODS: 30 male Wistar rats were randomized into three groups. Group A was treated with Methanolic extract of Hp (Jarsin®) via gastroesophageal catheter, and was submitted to cold swimming stress for 10 min/daily. Group B was submitted to cold stress, since group C served as control. Experiment duration was 10 days. Haematocrite and serum free fatty acids (FFA) were estimated. Furthermore volume and specific weight of each bone as well as bone mass density via dual energy X-Ray absorptiometry (DEXA) were measured. Statistic analysis by t-test. RESULTS: Hp treatment restores the stress injuries. Adrenals and bone mass density regain their normal values. CONCLUSIONS: Injuries occurring by forced swimming stress in the rats are significantly improved by Hp treatment. Estrogen-like effects of Hp flavonoids eventually may act favorable in bone remodeling.

Nifedipine-induced histological changes in the parotid glands of hypertensive rats.

Nifedipine is a widely used anti-anginal and anti-hypertensive agent. It is associated with significant gingival changes attributed more to collagen hyperplasia than to enhancement of protein synthesis. We investigated the influence of nifedipine on morphological changes in the parotid glands of rats in a model of hypertension. Twenty-eight male Wistar rats (8-10 weeks; 200±15 g) were divided into four groups (A-D). Hypertension was induced by surgical means in groups C and D. Animals in groups B and D were treated with nifedipine (0.85 mg/kg) via a gastroesophageal catheter the day after surgery (experimental day-1) for 2 weeks. A significant difference was observed between the control group and nifedipine group and between the control group and hypertension group with regard to the weight of the parotid gland and its surface area. Histological findings demonstrated changes in the parotid glands of hypertensive animals with mild vessel dilatation and infiltration of inflammatory cells. These histological findings seemed to be due more to changes in venous function than to alterations in gland architecture.

The influence of simvastatin in rats mandible and femur bone mass under Freund's adjuvant arthritis.

OBJECTIVES. Complete Freund's Adjuvant (CFA)-induced arthritis in rats has been used widely as a model of rodent arthropathy and polyarthritis followed by osteoporosis, decreased bone formation and increased bone formation. Osteoporosis is characterized by rapid reduce of bone mass affecting more than 100 million people worldwide. Periodontitis a chronic inflammatory, of multifactorian origin disease has been associated with general osteoporosis. Protective bone-specific anabolic and antiresorptive effects of HMG-CoA reductase inhibitors have also been evaluated in normal and osteoporotic bone. AIM. The aim of the study was to investigate mandible and femur bone density in Freund's adjuvant induced arthritis rats under the influence of simvastatin. METHODS. Three groups (A, B, C) of 7 Wistar male rats each aged 3 months, (292±48.38 g) were used. A control. Group B and C subjected experimental arthritis via complete Freund's adjuvant injected in right paw. Group C was treated with simvastatin 0.5 mg/kg/daily po 14 days. Femur, mandible were isolated and sizes parameters, biochemical serum findings and BMD were estimated. RESULTS. CFA established by paw diameter, adrenals and spleen weight increase and thymus weight decrease, while biochemical serum findings were also affected. Reduced femur, mandible weight and general bone mass parameters BMD evaluated via DEXA occurred and restored under simvastatin treatment. CONCLUSIONS. CFA induced mandible and femur injuries are repaired by ssimvatatin treatment that could be therapeutically useful.

Stress can affect drug pharmacokinetics via serum/tissues protein binding and blood flow rate alterations.

Binding of drugs to plasma and tissue proteins is critically involved in their pharmacokinetics and pharmacodynamics. Stress affects drugs' protein binding via alterations in plasma proteins' levels and excessive increase of free fatty acids due to cortisol-induced fat mobilisation. Free fatty acids play a crucial antagonistic role to drugs for the binding sites on albumin, the major binding plasma protein, resulting in subtherapeutic or toxic levels of many medications' pharmacological classes (oral anticoagulants, beta-lactames, fluoroquinolones, local anaesthetics). Upon stress, changes in blood flow rate and vascular function are also important parameters that can alter drug distribution and pharmacokinetics. Many cases are reported where stress-induced pharmacokinetic alterations led to serious clinical consequences. However, the stress affected drug activity do not always deteriorate the clinical outcome, due to the adaptive and defensive mechanisms of healthy organism. Sensitive population as patients with serious underlying diseases or after trauma or surgery should be given special attention. Clinicians should be alert and monitor cases where stress-induced drugs' pharmacokinetic modifications can have negative impact on the clinical outcome.

L-cysteine's effect on modulated rat brain enzymes with forced swimming.

BACKGROUND: Forced exercise is associated with oxidative stress, and L-cysteine (L-cys) administration reduces free-radical production. AIM: To investigate whether L-cys (5 mg/kg) intraperitoneal administration can ameliorate modulated total antioxidant status (TAS), protein concentration, and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase, and Mg2+-ATPase in rat brain after 2 and 3 hr of forced swimming. METHODS: TAS, protein, and enzyme activities were measured spectrophotometrically before and after 2 and 3 hr of exercise without or with L-cys administration. RESULTS: TAS concentration (55.6 +/- 1.5 vs. 42.1 +/- 1.0 vs. 37.4 +/- 1.2 micromol/L, p < .001), protein concentration (5.68 +/- 0.36 vs. 5.40 +/- 0.18 vs. 4.01 +/- 0.16 mg/ml, p < .01), and AChE activity (0.89 +/- 0.05 vs. 0.61 +/- 0.04 vs. 0.48 +/- 0.03 DeltaOD/min x mg protein, p < .001) were significantly reduced, whereas Na+,K+-ATPase (6.00 +/- 0.36 vs. 10.44 +/- 1.04 vs. 11.90 +/- 1.21 micromol phosphorus inorganic/hr x mg protein, p < .001) and Mg2+-ATPase activity (7.20 +/- 0.65 vs. 10.88 +/- 1.08 vs. 11.55 +/- 1.22 mmol phosphorus inorganic/hr x mg protein, p < .001) were statistically significantly increased after 2 and 3 hr of forced exercise. Post-L-cys administration, AChE activity was decreased (0.90 +/- 0.04 vs. 0.47 +/- 0.02 DeltaOD/min x mg protein, p < .001) and remained unaltered (0.64 +/- 0.04 vs. 0.67 +/- 0.04 DeltaOD/min x mg protein, p > .05) 2 and 3 hr postexercise (0.47 +/- 0.02 vs. 0.54 +/- 0.02 DeltaOD/min x mg protein, p > .05). Na+,K+-ATPase was decreased and remained unchanged (1.85 +/- 0.17 vs. 1.77 +/- 0.19 mumol phosphorus inorganic/hr x mg protein, p > .05) 2 and 3 hr postswimming (1.91 +/- 0.19 vs. 2.06 +/- 0.17 mumol phosphorus inorganic/hr x mg protein, p > .05). Mg2+-ATPase activity was similar with L-cys supplementation pre- vs. postswimming. CONCLUSIONS: L-cys administration might ameliorate modulated rat brain enzyme activities induced by free-radical production during forced swimming.

The role of the protein-binding on the mode of drug action as well the interactions with other drugs.

Drug transport and disposition are influenced by a non-specific and reversible drug binding to plasma and tissues proteins. Albumin and al acid glycoprotein are the most important transport proteins of the blood. Albumin possesses specific sites for acidic and basic drug binding and can interact with them in the plasma since a third site is trapped only by digoxin. Diseases and stress conditions induce conformational changes either in plasma or in tissue proteins by the synthesis of endogenous substances which can strong interfere with the amount of the free pharmacological effective drug ratio. This may affect the binding of drugs in target molecules inducing significant pharmacokinetic alterations. Stress conditions are associated with FFA increase in serum playing an antagonistic role with other acidic molecules (e.g. ampicillin) to the same binding site. The bounded drug is displaced and freer ratio is available to interact with various organ receptors leading to pharmacological effect enhancement and therefore to side effects manifestation such as seizures. Furthermore conjunctive tissues diseases, ageing, prolonged bleeding, starvation or diseases affecting protein profile, characterized by reduced total plasma proteins, followed by albumin decrease and lessen binding sites lead to more free drug availability enhancing its pharmacological effect. Increased a1-acid glycoprotein the acute phase protein as by heart infraction or liver morbidities (e.g CCl4 intoxication) mainly occupied from basic substances, in the case of cationic drug treatment resulted to the enhancement of them and consequently to pronounced effectiveness. In addition, renal failure reduced free fractions of many acidic drugs. It may be concluded that by narrowed therapeutic index of a medicine, and when drug/drug or drug/disease interactions are anticipated, drug monitoring seems to be necessary for its dosage adjustment.