Nicotinamide injection

Yamada, K., Nonaka, K., Hanafusa, T., Miyazaki, A., Toyoshima, H. and Tarui, S. (1982). Preventive and therapeutic effects of large-dose nicotinamide injections on diabetes associated with insulitis. Diabetes 31, 749-753. 

Fig. 2. Urinary glucose excretion in partially depancreatized rats with or without poly(ADP-ribose) synthetase inhibitor injection. 1, 2, and 3 months after the 90% pancreatectomy, the urine of each rat was collected for 24 h. Urinary glucose levels were measured by the glucose oxidase method. O Control rats nicotinamide-injected rats 3-aminobenzamide-injected rats. Statistical significance of differences between rats treated with and without poly(ADP-ribose) synthetase inhibitors was analyzed using Student s t test. Each point is the mean for five different rats vertical bars show SD when larger than the symbol indicating the mean value., and = p<0.10, p<0.05, and p<0.025 vs control rats. The time after the partial pancreatectomy is shown on the abscissa...

The injection of nicotinamide caused a striking rise in liver DPN 198, 199) in mice on an adequate diet and similar results also have been obtained with dogs ( 800) and with rats. The increase in the p3nidine coenzyme level following nicotinamide injection is not as marked in the rat as in the mouse 301). 

The rise in liver DPN in the mouse is correlated with the concentration of nicotinamide injected, as illustrated in Fig. 4. High concentrations (2000 mg/kg) of the amide are inhibitory to the synthesis of the DPN. The maximum increase is around tenfold and usually occurs from 8 to 10 hr following the administration of the nicotinamide the DPN level then returns to normal at the end of about 20 to 24 hr after the injection. It is of considerable interest to note that the pyridine nucleotide level always drops to the normal base level and not below the original value. 

Fig. 4. Effects of injecting different levels of nicotinamide on the liver DPN. The values represent the milligrams of nicotinamide injected per kilogram of body weight of the mouse. Taken from Kaplan et al. (199).

Riboflavin is widely used in the pharmaceutical, food-enrichment, and feed-supplement industries. Riboflavin USP is adininistered orally in tablets or by injection as an aqueous solution, which may contain nicotinamide or other solubilizers. As a supplement to animal feeds, riboflavin is usually added at concentrations of 2—8 mg/kg, depending on the species and age of the animal (see Feeds AND FEED ADDITIVES). 

As a consequence of the previous considerations Kieber et al. [75] have developed an enzymic method to quantify formic acid in non-saline water samples at sub-micromolar concentrations. The method is based on the oxidation of formate by formate dehydrogenase with corresponding reduction of /3-nicotinamide adenine dinucleotide (j6-NAD+) to reduced -NAD+(/3-NADH) jS-NADH is quantified by reversed-phase high performance liquid chromatography with fluorimetric detection. An important feature of this method is that the enzymic reaction occurs directly in aqueous media, even seawater, and does not require sample pre-treatment other than simple filtration. The reaction proceeds at room temperature at a slightly alkaline pH (7.5-8.5), and is specific for formate with a detection limit of 0.5 im (SIN = 4) for a 200 xl injection. The precision of the method was 4.6% relative standard deviation (n = 6) for a 0.6 xM standard addition of formate to Sargasso seawater. Average re-... 

Figure 4 Anterior whole-body scintigram of a patient injected with O.lpmol/kg (left) and a patient injected with O.Spmol/kg (right) four hours postinjection of 740 MBq Tc-hydrazino nicotinamide-polyethylene glycol-liposomes.

All potentials vs. screen-printed Ag/AgCl pseudo-reference, except values marked with asterisk ( ), which are vs. Ag/3M AgCl double-junction reference electrode, and values marked with dagger CfO, which are vs. saturated calomel. Abbreviations CoPC cobalt phthalocyanine, SPCE screen-printed carbon electrode, GOD glucose oxidase, MWCNT multi-walled carbon nanotubes, NAD nicotinamide adenine dinucleotide, PQQ pyrroloquinoline quinone, FIA flow injection analysis. 

Figure 7 shows the response of the redox potential in a perfused hamster liver to the addition of 45 mN ethanol. Instead of the vitro labeling strategy Just described. the pyridine nucleotide pools in this hamster liver were labeled vivo by intraperitoneal injection of 35 mg [5- C] nicotinamide 5 hours prior to sacrifice. The bottom two spectra (2.6 min and 12.8 min) were obtained prior to addition of ethanol. They show resonances from labeled NAD, natural abundance glycogen and natural abundance choline methyl groups of phospholipids but no resonance from reduced pyridine nucleotides. After addition of 45 mM 10% [1- C] ethanol (at 17.9 min), resonances from C-1 of ethanol and NADH are detectable. These data demonstrate that the pyridine nucleotide pools labeled by intraperitoneal injection are metabolically active and that addition of 45 mN ethanol results in a marked change in the redox potential of the liver as measured by NNR. Furthermore, the observation of separate resonances for the oxidized and reduced pyridine nucleotides indicates that chemical exchange between oxidized and reduced forms is slow on the NNR time scale, and demonstrate that NNR may be used to quantitate the redox potential of free pyridine nucleotides situ. 

Injected tryptophan causes a rise in erythrocyte DPN in the rat (562). The problem was taken up by Elvehjem and his school (c/. review, 224), who at first found tryptophan to be more active than nicotinamide in stimulating synthesis of rat-liver DPN and TPN (924, 925). Nicotinamide had, however, a sparing effect in young, but not in adult, rats (925). In pyridoxine deficiency conversion of tryptophan to pyridine nucleotides... 

T. Chow, S. Yoshida, M. Itoh, S. Hirose, and T. Takeda, Determination of Reduced Type Nicotinamide Adenine Dinucleotide by Flow Injection Analysis Using an Immobilized Enzyme Voltammetry System [in Japanese]. Bunseki Kagaku, 33 (1984) 310. 

K. Matsumoto, H. Ukeda, and Y. Osajima, Flow Injection Analysis of Reduced Nicotinamide Adenine Dinucleotide Using p-Naphthoquinone-4-Sulfonate as a Mediator. Agric. Biol. Chem., 48 (1984) 1879. 

M. Masoom and A. Townshend, Cyclic Regeneration of Nicotinamide Adenine Dinucleotide with Immobilized Enzymes. Flow-Injection Spectro-fluorimetric Determination of Ethanol. Anal. Chim. Acta, 185 (1986) 49. 

One mechanism that has been proposed to explain the hepatotoxicity of 1,1,2-trichloroethane is the generation of free radical intermediates from reactive metabolites of 1,1,2-trichloroethane (acyl chlorides). Free radicals may stimulate lipid peroxidation which, in turn, may induce liver injury (Albano et al. 1985). However, Klaassen and Plaa (1969) found no evidence of lipid peroxidation in rats given near-lethal doses of 1,1,2-trichloroethane by intraperitoneal injection. Takano and Miyazaki (1982) determined that 1,1,2-trichloroethane inhibits intracellular respiration by blocking the electron transport system from reduced nicotinamide adenine dinucleotide (NADH) to coenzyme Q (CoQ), which would deprive the cell of energy required to phosphorylate adenosine diphosphate (ADP) and thereby lead to depletion of energy stores. 

Rat injected with nicotinamide 4 hours prior to sacrifice. 

Fig. 1, from 7 days before the partial pancreatectomy, nicotinamide, at a dose of 0.5 g kg" body weight in 2 ml saline, and 3-aminobenzamide HCl, at a dose of 0.05 g kg" body weight in 2 ml saline, were injected intraperitoneally into each group of five rats every day. Nicotinamide and 3-aminobenzamide are inhibitors of pancreatic B-cell poly(ADP-ribose) synthetase the inhibitory ability of the latter is about tenfold as potent as that of the former [9]. The injection was continued until the 90th postoperative day. Five control rats received saline daily before and after the partial pancreatectomy. The residual pancreatic tissue, referred to as the remaining pancreas, was removed 3 months after the partial pancreatectomy and fixed in Bouin s solution. Hydrated 5 juni sections of paraffin-embedded pancreatic tissues were stained for insulin, glucagon, and somatostatin by the peroxidase antiperoxidase method [14]. 

Multivitamin preparations containing thiamine, riboflavin, pyridoxine, calcium pantothenate, nicotinamide, folic acid, and vitamin B12 also showed no loss in activity after irradiation and four years storage at 25°C. Such substances as aspirin for intravenous injection have been sterilized and also intravenous drip solutions, where less change in lactate and citrate solutions were produced than by autoclaving. 

The intraperitoneal injection of streptozotocin to mouse, rat, monkey, and dog induces diabetes. However, when a large amount of nicotinamide is administered before the administration of streptozotocin, the streptozotocin-induced diabetes is inhibited. This is also effective when nicotinamide is administered within 2 hr after the streptozotocin administration (17,18). The NAD content in P-cells of Langerhans islands in the pancreas is reduced by the administration of streptozotocin. However, this decrease does not occur after prior administration of a large amount of nicotinamide (19,20). The decrease in NAD content by streptozo-... 

Aminonicotinamide causes a disease similar to human pellagra (55) and the lethal effect of 6-aminonicotinamide is prevented by simultaneous injection of nicotinic acid or nicotinamide (56). Therefore, it is one of the putative pella-gragenic compounds. This antiniacin compound can be measured by using the... 

Amin and Reusch (89) described a rapid HPLC separation of pyridoxine, riboflavin, thiamine, and vitamin Bg. Separation has been reported to be complete within 3 min of injection. The work of Kothari and Taylor (90) provides yet another example of the use of HPLC in vitamin analysis for the phamaceutical industry. This method is suitable for simultaneous analysis of PN, thiamine, riboflavin, nicotinamide, and folic acid. This comprehensive vitamin analysis was possible by using a binary solvent program, which distinguishes this method from the above isocratic ones (Table 3). 

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