Renal protective effects of vicenin-2 and scolymoside in a mouse model of sepsis

This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata-vicenin-2 (VCN) and scolymoside (SCL)-could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury

Effect of tempol and tempol plus catalase on intra-renal haemodynamics in spontaneously hypertensive stroke-prone (SHSP) and Wistar rats.

Vasoconstriction within the renal medulla contributes to the development of hypertension. This study investigated the role of reactive oxygen species (ROS) in regulating renal medullary and cortical blood perfusion (MBP and CBP respectively) in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar rats. CBP and MBP were measured using a laser-Doppler flow meter before and after intra-renal infusion of tempol, the superoxide dismutase (SOD) mimetic or tempol plus catalase, the hydrogen peroxide-degrading enzyme. Tempol infusion significantly elevated blood perfusion within the renal medulla (MBP) in both SHRSP (by 43 ± 7%, P < 0.001) and Wistar rats (by 17 ± 2%, P < 0.05) but the magnitude of the increase was significantly greater in the SHRSP (P < 0.01). When the enzyme catalase and tempol were co-infused, MBP was again significantly increased in SHRSP (by 57 ± 6%, P < 0.001) and Wistar rats (by 33 ± 6%, P < 0.001), with a significantly greater increase in perfusion being induced in the SHRSP relative to the Wistar rats (P < 0.01). Notably, this increase was significantly greater than in those animals infused with tempol alone (P < 0.01). These results suggest that ROS plays a proportionally greater role in reducing renal vascular compliance, particularly within the renal medulla, in normotensive and hypertensive animals, with effects being greater in the hypertensive animals. This supports the hypothesis that SHRSP renal vasculature might be subjected to elevated level of oxidative stress relative to normotensive animals.

Pharmacologically induced ischemia-reperfusion syndrome in the rat small intestine.

BACKGROUND: Reports of ischemia-reperfusion (I/R) injury in vivo describe experiments in which lesions are induced by the physical procedure of clamping, (I/RIC). We compare this procedure with a pharmacologic technique in which I/R injury is induced by drug superfusion (I/RID). MATERIALS AND METHODS: We used rat intestine to determine whether the responses provoked by I/RIC, such as changes in reactive oxygen species (ROS) and nitric oxide levels, are also provoked by I/RID. To this end, rats were treated with allopurinol, SOD, catalase, L-NAME, and L-arginine. In both I/R models ischemia was maintained for 60 min, followed by 30 min of reperfusion. RESULTS: In both ischemia models, we observed significant differences in Evans blue (vascular permeability) and LDH (tissue injury) concentrations during the reperfusion period compared with the control group. I/RIC always induced greater injury. However, proportionally, the degree of protection was similar in the two models for the different treatments assayed. This indicates that the pathophysiologic mechanisms are the same. CONCLUSIONS: Our I/RID model induces a significant intestinal alteration during the reperfusion period and, also in general terms, this alteration is prevented or worsened in a similar and proportional way to that observed when using the classic I/RIC model. The I/RID model helps to explain the development and evolution of pathologies characterized by the induction of intermittent vasospasms that produce transitory reductions in vascular perfusion, which in turn can generate ROS though an I/R mechanism.

Efeito tóxico dos praguicidas maneb e paraquat sobre a atividade da enzima antioxidante catalase em ratos / Toxic effect of pesticides maneb and paraquat on catalase antioxidant enzyme activity in rats

Os radicais livres estão envolvidos em um grande número de enfermidades do ser humano.O cérebro tem níveis baixos de enzimas antioxidantes e um conteúdo lípidico elevado, tornando-se muito susceptível ao ataque de espécies reativas de oxigênio.Neste trabalho avaliou-se a lipoperoxidação em hipocampo e a atividade da enzima catalase em estriado e hipocampo de ratos tratados com o fungicida maneb (30 mg/kg) e o herbicida paraquat (10 mg/kg).Não houve alteração na lipoperoxidação nem na atividade enzimática no hipocampo dos animais tratados com ambos os praguicidas, porém foi observada uma inibição da catalase no estriado dos ratos tratados com maneb e com paraquat.Com estes resultados pode-se sugerir, de forma preliminar, uma ação tóxica maior sobre centros dopaminérgicos.Estudos sobre a toxicidade destes compostos são essenciais na compreensão do papel destes praguicidas e dos radicais livres na etiologia das doenças

Asma ocupacional por catalasa: A propósito de un caso / Catalase-induced occupational asthma: Report of one case

Estudio de un técnico de laboratorio que acude a nuestro centro con sintomatología clínica sugestiva de asma. El trabajador refiere una posible asociación con alérgenos presentes en su medio de trabajo. Dada la mejoría referida durante los fines de semana y períodos vacacionales, se decide llevar a cabo un estudio detallado, confirmando el diagnóstico de asma ocupacional por inhalación de polvo de catalasa (AU)

We report the case of a laboratory technician consulting because of clinical symptoms suggestive of bronchial asthma. The patient reported a possible association to allergens present in his occupational environment. The reported improvement over weekends and holiday periods leds us to carry out a detalled study, which confirmed the diagnosis of occupational asthma caused by catalase powder inhalation (AU)

[Activity of intracellular antioxidant enzymes in hypertensive patients]. / Aktivnost' vnutrikletochnykh antioksidantnykh fermentov u bol'nykh gipertonicheskoi bolezn'iu.

AIM: To assess activity of oxidation and function of cell antioxidant system in hypertensive patients. MATERIALS AND METHODS: 24 hypertensive patients (AP 140-180/95-114 mm Hg) were examined before and 4 weeks after standard therapy for plasmic levels of thiobarbituric acid (TBA) reacting products (TBARP), lipid peroxides (LP), total oxidant activity (TOA), total antioxidant activity (TAA) in red cells, activity of superoxide dismutase and catalase. A control group consisted of 16 healthy volunteers matched for age and sex. RESULTS: The patients had very high TAA and TBARP while the antioxidant status was subnormal. TOA/TAA was higher than in the controls. Clinically effective therapy with basic antihypertensive drugs lowered the oxidant activity and raised the antioxidant status while TOA/TAA index remained elevated. CONCLUSION: Hypertensive patients are exposed to apparent oxidant stress caused by imbalance between adaptive potential of intracellular enzyme antioxidant defense and activity of free radical processes. It is suggested that in pathogenesis of essential hypertension insufficiency of antioxidant enzymes results in development of chronic oxidant stress.

The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes.

The capacity of human phagocytes to generate superoxide anion (O2-), a free radical of oxygen, and a possible role for this radical or its derivatives in the killing of phagocytized bacteria were explored using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Superoxide dismutase, which removes O2-, consistently inhibited phagocytosis-associated nitroblue tetrazolium (NBT) reduction indicating the involvement of O2- in this process. Similarly, superoxide dismutase inhibited the luminescence that occurs with phagocytosis, implicating O2- in this phenomenon, perhaps through its spontaneous dismutation into singlet oxygen. Subcellular fractions from homogenates of both normal and CGD leukocytes generated O2- effectively in the presence of NADH as substrate. However, O2- generation by intact cells during phagocytosis was markedly diminished in nine patients with CGD. Leukocytes from mothers determined to be carriers of X-linked recessive CGD by intermediate phagocytic reduction of NBT elaborated O2- to an intermediate extent, further demonstrating the interrelationship between NBT reduction and O2- generation in phagocytizing cells. Activity of superoxide dismutase, the enzyme responsible for protecting the cell from the damaging effects of O2-, was approximately equal in homogenates of normal and CGD granulocytes. Polyacrylamide electrophoresis separated this activity into a minor band that appeared to be the manganese-containing superoxide dismutase associated with mitochondria and a more concentrated, cyanide-sensitive, cytosol form of the enzyme with electrophoretic mobility that corresponded to that of erythrocyte cuprozinc superoxide dismutase. Superoxide dismutase inhibited the phagocytic killing of Escherichia coli, Staphylococcus aureus, and Streptococcus viridans. A similar inhibitory effect was noted with catalase which removes hydrogen peroxide. Neither enzyme inhibited the ingestion of bacteria. Peroxide and O2- are believed to interact to generate the potent oxidant, hydroxyl radical (.OH). A requirement for .OH in the phagocytic bactericidal event might explain the apparent requirement for both O2- and H2O2 for such activity. In agreement with this possibility, benzoate and mannitol, scavengers of .OH, inhibited phagocytic bactericidal activity. Generation of singlet oxygen from O2- and .OH also might explain these findings. It would seem clear from these and other studies that the granulo cyte elaborates O2- as a concomitant of the respiratory burst that occurs with phagocytosis. To what extent the energy inherent in O2- is translated into microbialdeath through O2- itself, hydrogen peroxide, .OH, singlet oxygen, or some other agent remains to be clearly defined.