Summary
Arterial blood ketone body ratio (KBR) and hepatic mitochondrial phosphorylation rate (PR) were investigated in partially (70%) hepatectomized rats treated with 100 μg/kg body weight prostacyclin (PGI2) analogue i.p. after operation and every 12 h thereafter up to 72h. Sampling was performed at 12, 24, 48, and 72 h after operation. In sham-operated rats, KBR significantly increased from the preoperative values of 0.34±0.03 and 0.38±0.03, to 0.55±0.03 and 0.58±0.02 at 12 h in the groups with and without PGI2 treatment, respectively (P<0.001). KBR returned to the preoperative levels after 24 h in the PGI2-treated group, while it tended to be in the lower normal range in the untreated group. In the hepatectomized rats, KBR significantly decreased in the untreated group compared with the preoperative values and the values in the sham-operated group. It returned to the preoperative range within 72h. In the PGI2-treated group, KBR increased significantly, to values above 0.54, after a 24-h delay and was maintained at those levels for 72h. Concentrations of total ketone bodies (TKB) in the untreated groups remained in the upper range of preoperative values (above 200 nmol/ml) in the sham-operated rats and decreased significantly in the hepatectomized group (234 to 126 nmol/ml). TKB in the treated groups tended to decrease only in the sham-operated group (205 to 166 nmol/ml), and was massively reduced in the hepatectomized group (167 to 81 nmol/ml). PR was significantly enhanced after hepatectomy until 48h both in the groups with and without PGI2 treatment, but the degree of enhancement in PR was lower in the group with treatment than the one without treatment during the period of mitochondrial enhancement. It is suggested that PGI2 may convert the mitochondrial redox state toward oxidation accompanied by a suppression of ketogenesis and may activate the tricarboxylic acid (TCA) cycle. It is also suggested that PGI2 treatment may make it less necessary for mitochondria in the remnant liver to be enhanced to compensate the metabolic overload on the remnant liver and that PGI2 treatment may have a promoting effect on liver regeneration after hepatectomy.
Similar content being viewed by others
References
Araki H, Lefer AM (1980) Cytoprotective actions of prostacyclin during hypoxia in the isolated perfused cat liver. Am J Physiol 238: H176–181
Divald A, Ujhelyi E, Jeny A, Lapis K, Institoris L (1985) Hepatoprotective effects of prostacyclins on CCl4-induced liver injury in rats. Exp Mol Pathol 42: 163–166
Divald A, Vajta G, Olah J, Jeney A, Lapis K (1985) Effect of prostacyclin on triglyceride catabolism in CCl4 poisoned hepatocytes. IRCS (Int Res Commun Syst) Med Sci Libr Compend 13: 1117
Harano Y, Kosugi K, Hyosu T, Uno S, Ishikawa I, Shigeta Y (1983) Sensitive and simplified method for the differential determination of serum levels of ketone bodies. Clin Chim Acta 134: 327–336
Higgins GH, Anderson RM (1931) Experimental pathology of the liver. Restoration of the liver of the white rat following partial surgical remove. Arch Pathol 12: 186–202
Kamiyama Y, Ozawa K, Honjo I (1976) Changes in mitochondrial phosphorylative activity and adenylate energy charge of regenerating rabbit liver. J Biochem (Tokyo) 80: 875–881
Kimoto M, Shimahara Y, Ikai I, Wakashiro S, Ozaki N, Tatsumi Y, Tanaka A, Kamiyama Y, Yamaoka Y, Oazwa K (1989) The effects of PGI2 analog (OP-41483) on perfused porcine liver. Artif Organs 13: 204–208
Kiuchi T, Ozawa K, Yamamoto Y, Takayasu T, Maki A, Shimahara Y, Mori K, Kobayashi N, Yamaoka Y, Kumada K (1990) Changes in arterial ketone body ratio in the phase immediately after hepatectomy. Arch Surg 125: 655–659
Latipaa PM, Karki TT, Hiltunen JK, Hassinen IE (1986) Regulation of palmitoylcarnitine oxidation in isolated rat liver mitochondria: role of the redox state of NAD(H). Biochim Biophys Acta 875: 293–300
Mellanby J, Williamson DH (1974) Acetoacetate. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 1446–1451
Monden M, Fortner JG (1982) Twenty-four-and 48-hour canine liver preservation by simple hypothermia with prostacyclin. Ann Surg 196: 38–42
Mori K, Ozawa K, Yamamoto Y, Maki A, Shimahara Y, Kobayashi N, Yamaoka Y, Kumada K (1990) Response of hepatic mitochondrial redox state to oral glucose load—redox tolerance test as a new predictor of surgical risk in hepatectomy. Ann Surg 211: 438–446
Morimoto T, Taki Y, Jikko A, Yokoo N, Koizumi K, Nishihira T, Nishikawa K, Noguchi M, Tanaka A, Tanaka J, Ukikusa M, Kamiyama Y, Ozawa K (1986) Changes in oxidative phosphorylation, adenylate energy charge and respiratory components in chloramphenicoltreated regenerating rat liver. J Lab Clin Med 107: 194–198
Morimoto T, Ukikusa M, Taki Y, Koizumi K, Yokoo N, Tanaka A, Noguchi M, Yamamoto S, Nitta N, Kamiyama Y, Yamaoka K, Ozawa K (1988) Changes in energy metabolism of allografts after liver transplantation. Eur Surg Res 20: 120–127
Morimoto T, Kusumoto K, Isselhard W (1991) Impairment of grafts by short-term warm ischemia in rat liver transplantation. Transplantation 52: 424–431
Nakatani T, Yasuda K, Ozawa K, Tobe T (1984) Changes in blood glucose levels in relation to blood ketone body ratio following hypertonic glucose infusion in 70% hepatectomized rabbits. Eur Surg Res 16: 303–311
Nishikawa K, Nishihira T, Taki Y, Morimoto T, Yokoo N, Shimahara Y, Mori K, Yamaoka Y, Ozawa K (1988) Biological significance of enhanced ketogenesis in hepatectomized patients and aged rat liver mitochondria. Surg Res Commun 33: 251–261
Noda Y, Hughes RD, Williams R (1986) Effect of prostacyclin (PGI2) and a prostaglandin analogue BW 245C on galactosamine-induced hepatic necrosis. J Hepatol 2: 53–64
Ozaki N, Tokunaga Y, Wakashiro S, Ikai I, Morimoto T, Shimahara Y, Kamiyama Y, Yamaoka Y, Ozawa K, Nakase Y (1988) Evaluation of cytoprotective drugs for liver preservation by pyridine nucleotids fluorometry. Surger 104: 98–103
Ozawa K, Kitamura O, Mizukami T, Yamaoka Y, Kamano T, Takasan H, Honjo I (1972) Human liver motochondria. Clin Chim Acta 38: 385–393
Shikujara O, Monden M, Toyoshima K, Okamura J, Kosaki G (1983) Cytoprotective effect of prostaglandin I2 on ischemia-induced hepatic cell injury. Transplantation 36: 238–243
Shimahara Y, Kiuchi T, Yamamoto Y, Yamaguchi T, Takada Y, Amaoka Y, Kumada K, Nakatani T, Ozawa K (1990) Hepatic mitochondrial redox potential and nutritional support in liver insufficiency. In: Tanaka T, Okada A (eds) Nutritional support in organ failure. Elsevier, Amsterdam, pp 295–308
Taki Y, Morimoto T, Tanaka A, Noguchi M, Wang WY, Nishihira T, Nishikawa K, Mori K, Ozawa K (1990) Biological significance of enhanced mitochondrial ketogenesis during the early stages after 70% hepatectomy. J Surg Res 48: 56–60
Tobimatsu M, Toyoda K, Saito S, Ueda Y, Konomi K (1987) Effect of a stable prostacyclin analogue on canine renal allograft rejection. Ann Surg 205: 199–202
Williamson DH, Mellanby J (1974)D-(—)-3-Hydroxybutyrate. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 1840–1843
Yamamoto Y, Ozawa K, Okamoto R, Kiuchi T, Maki A, Lin H, Mori K, Shimahara Y, Kumada K, Yamaoka Y (1990) Prognostic implications of postoperative suppression of arterial ketone body ratio: time factor involved in the suppression of hepatic mitochondrial oxidation-reduction state. Surgery 107: 289–294
Author information
Authors and Affiliations
Additional information
Recipient of a research scholarship granted by the Alexander von Humboldt Foundation (Bonn, FRG)
Rights and permissions
About this article
Cite this article
Morimoto, T., Ozawa, K. & Isselhard, W. Conversion of mitochondrial redox state toward oxidation by prostacyclin in 70%-hepatectomized rats. Res. Exp. Med. 192, 161–168 (1992). https://doi.org/10.1007/BF02576271
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02576271