cytochrome-c-t and Endotoxemia

Recently, several studies have demonstrated that reactive oxygen species are responsible for inducing multiple organ failure and septic shock. Particularly, mitochondrial dysfunction has been demonstrated in the pathogenesis of multiple organ dysfunction syndrome (MODS). In cytopathic hypoxia, impairment of mitochondrial oxidative phosphorylation decreases aerobic adenosine triphosphate (ATP) production and potentially induces MODS. Shen-Fu (SF) injections are widely used in the treatment of various diseases. SF exhibits cardiovascular protective effects. For example, it can stretch the coronary artery, stabilize blood pressure, regulate IRI, and improve the overall heart function. Clinical studies have demonstrated that SF injections have notable therapeutic effects on septic and hemorrhagic shocks. In the present study, the effects of SF injection on mitochondrial function in the intestinal epithelial cells of rats with endotoxemia were analyzed.

Topics: Animals; Cytochromes c; Cytokines; Drugs, Chinese Herbal; Endotoxemia; Epithelial Cells; Injections, Intravenous; Intestine, Small; Male; Membrane Potential, Mitochondrial; Mitochondria; Rats, Sprague-Dawley

Bacterial Lipopolysaccharide (LPS) induced inflammation is implicated in the infection associated testicular tissue damage. Earlier, using a LPS induced acute endotoxemic rat model, we have shown the involvement of inflammation-induced oxidative stress in the impaired steroidogenesis and spermatogenesis. In the present study, we report a significant induction (more than 2-fold) of stress response proteins HSP-60, HMGB-1 and 2 in the testes, as early as 6 h after LPS injection with a later decrease. This induction of acute stress is closely followed by a significant reduction (74%) in Bcl2/Bax ratio along with leakage of cytochrome c (3 fold increase, p < 0.05) from mitochondria and increased caspase-3 activity levels (2.9 fold, p < 0.05) at 12 h and 24 h post LPS injection respectively. Further studies on PARP cleavage revealed a pattern similar to necrotic death during early periods (3 h to 24 h) and apoptosis at later periods (24 h to 72 h) after LPS treatment. In conclusion, the present study shows the involvement of stress response proteins and mitochondrial dysfunction in LPS-induced germ cell death in male rats.

Topics: Acute Disease; Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Chaperonin 60; Cytochromes c; Endotoxemia; Endotoxins; HMGB1 Protein; HMGB2 Protein; Leydig Cells; Male; Mitochondria; Orchitis; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Spermatogenesis

The rostral ventrolateral medulla (RVLM) is the origin of a 'life-and-death' signal that reflects central cardiovascular regulatory failure during brain stem death. Using an experimental endotoxaemia model, we evaluated the hypothesis that the 60 kDa heat shock protein 60 (HSP60) reduces cardiovascular fatality during brain stem death via an anti-apoptotic action in the RVLM. In Sprague-Dawley rats maintained under propofol anaesthesia, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg(-1)). Pretreatment with a microinjection of actinomycin D or cycloheximide into bilateral RVLM significantly blunted this HSP60 increase, whereas real-time PCR showed progressive augmentation of hsp60 mRNA. Intriguingly, superimposed on the augmented expression was a progressive decline in mitochondrial, or elevation in cytosolic, HSP60 in ventrolateral medulla. Loss-of-function manipulations in the RVLM using anti-HSP60 antiserum or antisense hsp60 oligonucleotide exacerbated mortality by potentiating the cardiovascular depression during experimental endotoxaemia, alongside intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone-associated DNA fragments or augmented cytochromec-caspase-3 cascade of apoptotic signalling in the RVLM. Immunoprecipitation coupled with immunoblot analysis further revealed a progressive increase in the complex formed between HSP60 and mitochondrial or cytosolic Bax or mitochondrial Bcl-2 during endotoxaemia, alongside a dissociation of the cytosolic HSP60-Bcl-2 complex. We conclude that HSP60 redistributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxaemia via reduced activation of the cytochrome c-caspase-3 cascade of apoptotic signalling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl-2.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Stem; Cardiovascular System; Caspase 3; Caspases; Chaperonin 60; Cytochromes c; Death; Endotoxemia; Escherichia coli; Gene Expression Regulation; Male; Medulla Oblongata; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; RNA, Messenger

The local anesthetic richlocaine decreased the area of necrosis in the skin flap under conditions of reduced blood flow by 29.5%. Improved survival of skin flap after richlocaine treatment alleviated endogenous intoxication, reduced secondary inflammatory reaction, improved liver function, and normalized the ratio between vasoconstricting and vasodilating prostaglandins. This effect was most pronounced after combination therapy with richlocaine and direct-action antihypoxant energostim.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Cell Survival; Cytochromes c; Drug Combinations; Endotoxemia; Erythrocytes; Histamine; Hydroxyproline; Hypoxia; Inflammation; Inosine; Keratinocytes; Lactates; Male; NAD; Necrosis; Piperidines; Rats; Regional Blood Flow; Serotonin; Skin; Surgical Flaps; Time Factors; Vasodilator Agents