Changes in mitochondrial activity caused by ammonium salts and the protective effect of carnitine

Bellei, Monica; Battelli, Daniele; Guarriero, D.M.; Muscatello, Umberto; DiLisa, Fabio; Siliprandi, N.; Bobyleva-Guarriero, Valentina

doi:10.1016/s0006-291x(89)80195-0

Cited by 28 publications

(8 citation statements)

References 16 publications

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“…It appears that the protective mechanism of carnitines has a multifactorial character. Promising neuroprotective effects of carnitines were shown during metabolic inhibition induced by ammonia intoxication20 or ischemia‐hypoxia 5. The authors suggest that neuroprotective effects were achieved through mitochondrial energy enhancement by using alternative energy sources, such as ketone bodies.…”

Section: Discussionmentioning

confidence: 99%

Effect of l‐Carnitine Pretreatment on 3‐Nitropropionic Acid‐Induced Inhibition of Rat Brain Succinate Dehydrogenase Activity

Binienda

Sadovova

Rountree

et al. 2001

Annals of the New York Academy of Sciences

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l‐Carnitine (LC) plays an important regulatory role in the mitochondrial transport of long chain free fatty acids (FFA). 3‐Nitropropionic acid (3‐NPA) is known to induce cellular energy deficit and oxidative stress‐related neurotoxicity via an irreversible inhibition of mitochondrial succinate dehydrogenase (SDH). In the present study, activity of SDH was measured in order to evaluate neuroprotective effects of LC against the 3‐NPA‐induced neurotoxicity. Male, CD Sprague‐Dawley rats, three months old, were injected with either 50 or 100 mg/kg of LC, i.p., 30 min prior to 3‐NPA (30 mg/kg, s.c.) or with 3‐NPA alone. The activity of brain SDH was quantified spectrophotometrically in caudate nucleus (CN), frontal cortex (FC), and hippocampus (HIP) 60 min after the 3‐NPA injection. The SDH activity in the animals treated with 3‐NPA alone was 38% (CN), 50% (FC), and 36% (HIP) that of saline controls. Pretreatment with LC prior to 3‐NPA injection attenuated decreases of SDH activity by approximately 15 and 29% (LC low and high dose, respectively). Despite the attenuation of SDH inhibition, the activity of SDH in these regions remained significantly lower in treated than in control rats (p < 0.05). It appears that the protective effect of LC against 3‐NPA‐induced oxidative stress cannot be explained by the direct action of LC to interfere with the SDH inhibition but are rather achieved by LC actions downstream of the SDH inhibition.

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Section: Discussionmentioning

confidence: 99%

Effect of l‐Carnitine Pretreatment on 3‐Nitropropionic Acid‐Induced Inhibition of Rat Brain Succinate Dehydrogenase Activity

Binienda

Sadovova

Rountree

et al. 2001

Annals of the New York Academy of Sciences

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“…l ‐Carnitine prevents the decrease in the brain energy metabolites ATP and phosphocreatine 33 . It stimulates the hepatic urea cycle and normalizes α‐ketoglutarate oxidation, partially improving mitochondrial function, probably even through improved pyruvate oxidation and tricarboxylic acid flux cycle 33,34 . l ‐Carnitine positively influences ammonia catabolism.…”

Section: Discussionmentioning

confidence: 99%

“…33 It stimulates the hepatic urea cycle and normalizes a-ketoglutarate oxidation, partially improving mitochondrial function, probably even through improved pyruvate oxidation and tricarboxylic acid flux cycle. 33,34 l-Carnitine positively influences ammonia catabolism. One theory underlines the importance of the accumulation of glutamate, the most important by-product of ammonia in the brain, as a possible cause of HE.…”

Section: Discussionmentioning

confidence: 99%

EFFECTS OF A SINGLE, SHORT INTRAVENOUS DOSE OF ACETYL‐l‐CARNITINE ON PATTERN‐REVERSAL VISUAL‐EVOKED POTENTIALS IN CIRRHOTIC PATIENTS WITH HEPATIC ENCEPHALOPATHY

Siciliano

Annicchiarico

Lucchese

et al. 2006

Clin Exp Pharma Physio

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1. In animals and in cultured neurons, L-carnitine and acetyl-L-carnitine (ALCAR) have been shown to counteract some of the toxic effects of ammonia. In order to detect similar properties in humans, we studied neuronal function after ALCAR administration in cirrhotics with hepatic encephalopathy (HE). 2. Eighteen cirrhotic patients with persistent HE and hyperammonaemia were investigated in the present study and six subjects with a prior transient ischaemic attack were used as controls. 3. The prominent positive component that occurs approximately 100 msec after the pattern reversal (P100) latencies of visual-evoked potentials were used to evaluate neuronal function. At first, the P100 latency was measured in six cirrhotic patients with HE and in the six controls before the administration of 0.5 g ALCAR in 50 mL isotonic saline (infusion rate 10 mL/min) and 15, 30, 60 and 90 min later. 4. A significant reduction in P100 latencies was identified 30 min after ALCAR infusion in HE patients, whereas no differences were observed in controls. 5. Thereafter, the P100 latency was evaluated in the 12 other cirrhotic patients with HE only before and 30 min after ALCAR infusion. The mean of the P100 latencies measured in these subjects was significantly shorter after ALCAR infusion compared with values obtained before ALCAR administration (mean (+/-SD) 130.78 +/- 5.50 vs 136.08 +/- 6.45 msec, respectively; P = 0.0013). 6. The present study suggests that a single intravenous dose of ALCAR may transiently improve neuronal function in cirrhotic patients with persistent HE and hyperammonaemia.

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“…Biochemically, ALC acts as a carrier of fatty acids across the inner mitochondrial membrane for their subsequent beta-oxidation (12). It has been found that acetyl-L-carnitine hydrochloride increases the metabolic rate of mitochondria, improving the mitochondrial utilisation of oxygen (4,24). ALC enhances the utilisation of alternative sources of energy (1).…”

Section: Discussionmentioning

confidence: 99%

Effect of Acetyl-L-Carnitine on Leukemia L1210 Resistant to Mitoxantrone

Niang

Mĕlka²

2000

Acta Med. (Hradec Kralove, Czech Repub.)

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Supportive care in tumour chemotherapy is a subject of intensive research. The complications of cytostatic therapy are a cause of extensive research of their pharmacological interactions and side effects. The immunologic and biochemical changes accompanying tumours are the factor that is most responsible for the worsening of the physiology of the host. Regimens containing carnitine and it’s acetyl-derivative are used in many cases, among others even for preventing hepatotoxicity. Our hypothesis was to verify the supporting metabolic effects of acetyl-L-carnitine hydrochloride (ALC) in combined therapy with mitoxantrone (MX) and hepatotoxic cytostatic drugs including alkylating agents. This present report describes the effect of ALC in combination with MX on DBA/2 male mice bearing a transplantable L1210 leukemia resistant to MX. The criterion for evaluation of effect was the length of survival time of experimental animals. The proportional- hazards model quadratic in the drug dose (7) was used for survival time evaluation and optimal dose calculation. The hazard functions and the index of relative hazard were determined using Weibull distribution after logarithmic transformation of the entered data in each particular group. The dose-response curve was represented by a second-degree polynomial without absolute term. The combination therapy revealed that the optimal dose of ALC was 186 mg/kg s.c. This relation is shown in Fig.1. A significant effect of ALC (s.c.) in combined therapy with MX (6 mg/kg i.v.) given to animals bearing an experimental form of leukemia L1210/MX resistant to MX was proven at a level of probability p≤ 0.001. The effect of ALC in monotherapy was not demonstrable.

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Changes in mitochondrial activity caused by ammonium salts and the protective effect of carnitine

Cited by 28 publications

References 16 publications

Effect of l‐Carnitine Pretreatment on 3‐Nitropropionic Acid‐Induced Inhibition of Rat Brain Succinate Dehydrogenase Activity

Effect of l‐Carnitine Pretreatment on 3‐Nitropropionic Acid‐Induced Inhibition of Rat Brain Succinate Dehydrogenase Activity

EFFECTS OF A SINGLE, SHORT INTRAVENOUS DOSE OF ACETYL‐l‐CARNITINE ON PATTERN‐REVERSAL VISUAL‐EVOKED POTENTIALS IN CIRRHOTIC PATIENTS WITH HEPATIC ENCEPHALOPATHY

Effect of Acetyl-L-Carnitine on Leukemia L1210 Resistant to Mitoxantrone

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