Sodium nitroprusside-induced tissue hypoxia and its correction with plant preparations

Abstract

Tissue hypoxia caused by acute or repeated administration of sodium nitroprusside to experimental mice induced changes in hemopoietic and lymphoid organs. Isolated flavonoids and alkaloids as well as complex plant preparations abolished the negative consequences caused by the hypoxant and prolonged the lifespan of experimental animals.Tissue hypoxia is characterized by disturbed utilization of oxygen for biooxidation by cells and reduced efficiency of entrapping free energy released during biooxidation, which is usually associated with uncoupling of oxidation and phosphorylation [2]. The hypoergic state activates free-radical processes and impairs antioxidant defense. LPO products damage biomembranes (including mitochondrial membanes) and aggravate energy metabolism disturbances, i.e. a vicious circle is thus forming. It is known that sodium nitroprusside (SN) is a donator of nitric oxide (NO) and in high concentrations induces tissue hypoxia [11]. Endogenous NO is involved in various physiological and cell responses, but can be a pathological factor in neurogenic pathologies of CNS, ischemia, brain stroke, convulsive disorders [9].We previously demonstrated stress-inducing effects of hypoxia of various geneses and the possibility of its correction with plant-derived preparations [6]. It is well known that many natural bioactive substances (e.g. flavonoids and alkaloids) produce an antioxidant effect and improve the resistance to hypoxia [10]. Plant preparations and bioactive substances isolated from plants can be used as correctors in acute and repeated tissue hypoxia, which was the subject of the present study. MATERIALS AND METHODSThe experiments were carried out on 120 male and female outbred mice and 34 female CBA mice obtained from the Department of Biomedical Modeling, Institute of Pharmacology, Tomsk Research Center, Siberian Division of Russian Academy of Medical Sciences. The animals were kept in accordance with European Convention on Protection of Vertebrate Animals Used in Experimental and Scientific Purposes (Strasbourg, 1986). Acute tissue hypoxia was modeled in mice by intraperitoneal injection of 25 mg/kg SN [7]. Plant preparations were administered per os for 5 days (prophylactic course), the last dose was given 1 h before hypoxic exposure. The animals received 0.6 and 2.5 mg/kg delphinium (Delphinium elatum) tincture, 0.12 and 0.25 delphinium extract, 0.05 and 1.50 mg/kg delphinium alkaloids, 2 ml/kg tincture from poison hemlock (Conium maculatum) dry herb, 2 ml/kg tincture from wet poison hemlock herb, 1 ml/kg tincture from dry poison hemlock inflorescences, 2 ml/kg tincture from fresh poison hemlock inflor-