The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners.

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The functional thyroid status of hexachlorobenzene (HCB)-treated rats was studied. HCB caused a depletion of serum thyroxine (T4), but did not change L-3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the thyroid regulated mitochondrial enzyme L-glycerolphosphate dehydrogenase (LGPD) and cytosolic enzymes, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were assayed in livers of normal and HCB (100 mg/100 g bw) treated Wistar rats. Mitochondrial LGPD activity did not change significantly, however ME, 6GPD and G6PD were induced by HCB only in non-thyroidectomized animals. The absence of cytosolic enzymes induction in thyroidectomized rats treated with HCB indicates that HCB is not intrinsically thyromimetic. The induction of hepatic ME, G6PD and 6PGD activities in HCB thyroidectomized rats was dependent on the presence of thyroid hormone. The unchanged activity of mitochondrial LGPD in contrast to the increased activities of the cytosolic enzymes ME, G6PD and 6PGD is not consistent with a shift in functional thyroid status following HCB treatment.

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The effect of hexachlorobenzene (HCB) (1 g/kg bw) administration for 4 weeks, on thyroxine (T4) and triiodothyronine (T3) metabolism was studied in Wistar rats. The effect on serum binding of T4 has also been studied. Animals were injected with a tracer dose of either labeled hormone and by examining serum L-125I-T4 and L-125-I-T3, kinetics of radiolabeled hormones metabolism were calculated. The T4 metabolic clearance (MCI) as well as the distribution space, were increased by 6 fold. Decreased serum T4 levels result from an increase both in deiodinative and fecal disposal in HCB-treated rats. 125I-T3 metabolism was slightly affected. The enhanced peripheral disposition of thyroxine appears to lead to increased thyroid function, as measured by augmented TSH serum levels and 125I-thyroidal uptake. Serum binding of T4 was not affected.

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